Mariana Cúri

A family study of early-onset obsessive-compulsive disorder.

Results from family studies have suggested that obsessive‐compulsive disorder (OCD) is a genetically heterogeneous disorder and have emphasized the importance of identifying valid subgroups of patients. The current study focused on early‐onset OCD probands and examined the recurrence risks of OCD and tics among first‐degree family members. One hundred six children and adolescents with OCD were recruited from a specialty clinic for OCD and 44 control individuals without OCD were identified by random‐digit dialing. These 150 probands and their 465 first‐degree relatives were assessed by trained interviewers, using standardized semi‐structured interviews. Diagnoses were assigned according to DSM‐IV criteria by two experts blind to the probands diagnosis, through the best‐estimate process. These data were analyzed using χ2 tests, t‐tests, logistic regression, and generalized estimating equations (GEE). Case probands had a mean age of onset of OC symptoms of 6.7 years (SD = 2.8), and high comorbid rates with Tourette syndrome (33%) and chronic tics (13.2%). Compared to control relatives, case relatives had higher age‐corrected recurrence risks of OCD (22.7% vs. 0.9%, odds ratio (OR) = 32.5, 95% confidence interval (CI) = 4.5–230.8, P = 0.0005), and chronic tics (11.6% vs. 1.7%, OR = 7.9, 95% CI = 1.9–33.1, P = 0.005). A comorbid diagnosis of tics in the relatives was the best predictor of their diagnosis of OCD (OR = 7.35, 95% CI = 3.79–14.25, P < 0.0001). There was a significant correlation between the ages of onset of OCD in probands and their affected relatives. Childhood onset OCD is a highly familial disorder. Some early‐onset cases may represent a valid subgroup, with higher genetic loading and shared vulnerability with chronic tic disorders.

Prenatal, Perinatal, and Postnatal Risk Factors in Obsessive–Compulsive Disorder

BACKGROUND The etiology of obsessive-compulsive disorder (OCD) remains unknown, although it is thought to involve an interaction of genetic and environmental factors. This study aimed to identify prenatal, perinatal, and postnatal risk factors in OCD. METHODS We compared retrospectively 68 OCD patients to 70 control subjects based on responses given on a standardized questionnaire. The questionnaire was designed to evaluate environmental factors, with a special focus on gestation, labor, birth, and early infancy aspects. RESULTS The group of OCD patients had risk factors with greater frequency than the control group. Notable among the significant findings (p < or = 0.001) were edema of the hands, feet, or face and excessive weight gain during gestation; hyperemesis gravidarum; prolonged labor; preterm birth; and jaundice. When socioeconomic class was used as a covariable in the logistic regression analysis, prolonged labor and edema during pregnancy remained statistically significant. CONCLUSIONS Some early risk factors may be associated with the expression of OCD later in life such as edema during pregnancy and prolonged labor. If our findings are confirmed in future studies, greater attention should be given to such factors in predisposed individuals, especially in prenatal care and delivery.

Obsessive-Compulsive Spectrum Disorders and Rheumatic Fever: A Family Study

BACKGROUND Obsessive-compulsive spectrum disorders (OCSDs) are more frequent in patients with active or prior rheumatic fever (RF), suggesting that OCSD and RF may share underlying etiologic mechanisms. Our objective was to estimate the frequency of OCSD in first-degree relatives (FDRs) of RF patients and controls to determine whether there is a familial relationship between OCSD and RF. METHODS This is a case-control family study. Of the 98 probands included in this study, 31 had RF without Sydenhams chorea (SC) and had 131 relatives, 28 had RF with SC and had 120 relatives, and 39 were controls without RF. All probands, 87.9% of the RF FDRs and 93.7% of the control FDRs were assessed directly with structured psychiatric interviews and best-estimate diagnoses were assigned. Odds ratios of morbid risks were estimated using logistic regression by the generalized estimating equations (GEE) method and compared between groups. RESULTS The rate of OCSDs was significantly higher among FDRs of RF probands than among FDRs of controls (n=37; 14.7% vs. n=10; 7.3%, i=.0279). A diagnosis of OCSDs in an RF proband was associated with a higher rate of OCSDs among FDRs when compared to control FDRs (p-GEE=.02). There was a trend for a higher rate of OCSDs among FDRs of RF probands presenting no OCSD, although the difference was not significant (p-GEE=.09). CONCLUSION The results are consistent with the hypothesis that a familial relationship exists between OCSD and RF, since an OCSD in the RF proband was found to increase the risk of OCSDs among FDRs. Additional neuroimmunological and genetic studies involving larger samples are needed to further elucidate this apparent familial relationship between RF and OCSD.

Obsessive–compulsive symptoms in sibling pairs concordant for obsessive–compulsive disorder†‡

Obsessive–compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. Phenotypic studies of affected sib‐pairs (SPs) may help to characterize familial components of the phenotype. To determine whether SPs affected with OCD are similar in age at onset of obsessive–compulsive symptoms (OCS), symptom dimensions and presence of tic disorders (TDs). Forty OCD siblings ranging from 13 to 59 years old were evaluated by expert psychiatrists or psychologists. Families with two or more siblings affected with OCD were recruited from several OCD clinics in Brazil. The Yale Brown Obsessive–Compulsive Scale Checklist was used to assess OCS and the severity of OCD. The OCD diagnoses were made according to the DSM‐IV. The chi‐square test was used to assess concordance of TD presence within SPs based on the TD frequency reported in the literature (30%). There were significantly more siblings with early‐onset OCS than with late‐onset OCS (P = 0.002). Age at onset of OCS correlated positively and significantly between the two members of each SP (P = 0.005). Fourteen patients (35%) were diagnosed with TDs. There was no concordance of the TD presence within the SPs. When both were male, there was a significant sibling correlation in the contamination obsessions/cleaning compulsions dimension (ICC = 0.74; P = 0.002). Similarly, when both siblings were female, they were comparable in the hoarding obsessions/compulsions dimension (ICC = 0.76; P = 0.01). Familial factors seem to contribute to specific OCD phenotypic components such as age at onset of OCS and specific dimensions. The obvious influence of gender is as yet unexplained.

Low coronary driving pressure early in the course of myocardial infarction is associated with subendocardial remodelling and left ventricular dysfunction

Subendocardial remodelling of the left ventricular (LV) non‐infarcted myocardium has been poorly investigated. Previously, we have demonstrated that low coronary driving pressure (CDP) early postinfarction was associated with the subsequent development of remote subendocardial fibrosis. The present study aimed at examining the role of CDP in LV remodelling and function following infarction. Haemodynamics were performed in Wistar rats immediately after myocardial infarction (MI group) or sham surgery (SH group) and at days 1, 3, 7 and 28. Heart tissue sections were stained with HE, Sirius red and immunostained for α‐actin. Two distinct LV regions remote to infarction were examined: subendocardium (SE) and interstitium (INT). Myocyte necrosis, leucocyte infiltration, myofibroblasts and collagen volume fraction were determined. Compared with SH, MI showed lower CDP and LV systolic and diastolic dysfunction. Necrosis was evident in SE at day 1. Inflammation and fibroplasia predominated in SE as far as day 7. Fibrosis was restricted to SE from day 3 on. Inflammation occurred in INT at days 1 and 3, but at a lower grade than in SE. CDP correlated inversely with SE necrosis (r = −0.65, P = 0.003, at day 1), inflammation (r = −0.76, P < 0.001, at day 1), fibroplasia (r = −0.47, P = 0.04, at day 7) and fibrosis (r = −0.83, P < 0.001, at day 28). Low CDP produced progressive LV expansion. Necrosis at day 1, inflammation at days 3 and 7, and fibroplasia at day 7 correlated inversely with LV function. CDP is a key factor to SE integrity and affects LV remodelling and function following infarction.

The long-term outcome of patients with hypertensive cardiomyopathy

The prognosis of dilated cardiomyopathy due to hypertension (HT-DCM) is surprisingly unknown, particularly in the absence of coronary disease and diabetes. We aimed at investigating the long-term outcome and the predictors of mortality in patients with left ventricular systolic dysfunction exclusively due to hypertension. From October 1995 to May 2001, 90 consecutive patients with echocardiographic fractional shortening (FS) <30% and 29 control patients with FS ⩾30% were included. Obstructive coronary disease was excluded by dipyridamole myocardial perfusion imaging in all patients and coronary angiography in 60. After a mean follow-up of 4.3±1.6 years, the total mortality rate of HT-DCM was twice as much higher than that of patients without left ventricular systolic dysfunction (P=0.01). In HT-DCM, the 5-year mortality rate was 26%. Univariate analyses selected age and creatinine for being positively related to mortality, and body mass index, FS and blood pressure during follow-up for being negatively related to mortality. Neither the improvement of left ventricular FS nor the decrease in left ventricular mass index was related to survival. Multivariate analysis identified (hazard ratio; 95% confidence interval) age (1.08; 1.02–1.13), body mass index (0.86; 0.75–0.98), and baseline FS (0.88; 0.78–0.98) as independent predictors of mortality. In conclusion, poor survival in HT-DCM can be anticipated by the severity of left ventricular systolic dysfunction and advanced age. Instead of ominous signs, high blood pressure and body mass may predict a more favourable prognosis.

Left ventricular hypertrophy predicts outcome of hypertension regardless of the type of ventricular arrhythmia present

Left ventricular hypertrophy is associated with an increased cardiovascular mortality in hypertension. A potential role of ventricular arrhythmias is debated but not yet determined. The purpose of this study was to evaluate whether the presence of arrhythmias would ascribe any additional risk to cardiovascular mortality beyond that related to the presence of left ventricular hypertrophy. From November 1988 to February 1991, 40 mild to severe hypertensive patients (mean SBP, DBP 183/117 mm Hg) were submitted to clinical, echocardiographic and electrocardiographic evaluations complemented by 24-h Holter monitoring and then followed until November 1996. The Kaplan–Meier method supplemented by the Cox multiple regression model were performed to identify the variable(s) associated with fatal cardiovascular outcome. Twelve cardiovascular fatalities occurred as a consequence of sudden death (n = 4), stroke (n = 4), heart failure (n = 2) and myocardial infarction (n = 2). In comparison with patients who survived, those dying from cardiovascular causes had a greater percentage of electrocardiographic left ventricular hypertrophy (83 vs 36%, P = 0.0037) and couplets of ventricular ectopic beats (58 vs 18%, P = 0.0467). In addition, they showed larger left ventricular diastolic diameter (60 ± 10 vs 53 ± 8 mm), mass index (248 ± 67 vs 154 ± 57 g/m2) and posterior wall thickness (12 ± 2 vs 10 ± 2 mm), as well as shorter left ventricular fractional shortening (0.23 ± 0.8 vs0.32 ± 0.9). Univariate analysis showed that electrocardiographic left ventricular hypertrophy and strain, mass index, end-systolic wall stress, fractional shortening and the presence of couplets were significantly related to cardiovascular mortality. However, only mass index was shown to be independently associated with cardiovascular death. In conclusion, left ventricular hypertrophy predicts cardiovascular outcome, regardless of the presence of other signs of cardiac damage, including ventricular arrhythmia.

Anxiety Disorders and Rheumatic Fever: Is There an Association?

INTRODUCTION Findings suggest that obsessive-compulsive disorder (OCD) and related disorders, referred to as obsessive-compulsive spectrum disorders (OCSDs), are more common in patients with rheumatic fever (RF). OBJECTIVES To determine whether RF or Sydenhams chorea increases the probability of anxiety disorders in the relatives of individuals with RF with and without SC. METHODS This was a case-control family study in which 98 probands and 389 first-degree relatives (FDRs) were assessed using structured psychiatric interviews. A Poisson regression model was used to determine whether the presence of any disorder in one family member influences the rate of disorders in the remaining family members. RESULTS Generalized anxiety disorder (GAD) occurred more frequently in the FDRs of RF probands than in those of control probands (P=.018). The presence of RF, GAD, or separation anxiety disorder in one family member significantly increased the chance of OCSDs in another member of the family. CONCLUSION We found familial aggregation among RF, GAD, and OCSDs. Clinicians should be aware of the possible familial relationship between GAD and OCSDs in their RF patients and their family members, which may suggest a genetic component between them. Further studies on OCD should include anxiety disorders to better define OCD spectrum.

A model for psychiatric questionnaires with embarrassing items.

We propose an item response theory model to analyse psychiatric questionnaires that contain embarrassing items. We use Bayesian methods to estimate its parameters and consider a simulation study to evaluate the performance of the proposed estimators. The results are illustrated with the analysis of data collected to evaluate teenager depression, highlighting the gender difference in the probabilities of ‘crying crisis’, a trait known to embarrass some male populations.

Subendocardial fibrosis in remote myocardium results from reduction of coronary driving pressure during acute infarction in rats

OBJECTIVE To investigate the role of hemodynamic changes occurring during acute MI in subsequent fibrosis deposition within non-MI. METHODS By using the rat model of MI, 3 groups of 7 rats each [sham, SMI (MI <30%), and LMI (MI >30%)] were compared. Systemic and left ventricular (LV) hemodynamics were recorded 10 minutes before and after coronary artery ligature. Collagen volume fraction (CVF) was calculated in picrosirius red-stained heart tissue sections 4 weeks later. RESULTS Before surgery, all hemodynamic variables were comparable among groups. After surgery, LV end-diastolic pressure increased and coronary driving pressure decreased significantly in the LMI compared with the sham group. LV dP/dt max and dP/dt min of both the SMI and LMI groups were statistically different from those of the sham group. CVF within non-MI interventricular septum and right ventricle did not differ between each MI group and the sham group. Otherwise, subendocardial (SE) CVF was statistically greater in the LMI group. SE CVF correlated negatively with post-MI systemic blood pressure and coronary driving pressure, and positively with post-MI LV dP/dt min. Stepwise regression analysis identified post-MI coronary driving pressure as an independent predictor of SE CVF. CONCLUSION LV remodeling in rats with MI is characterized by predominant SE collagen deposition in non-MI and results from a reduction in myocardial perfusion pressure occurring early on in the setting of MI.