Neuroprotective effect of oral choline administration after global brain ischemia in rats.

Choline - now recognized as an essential nutrient - is the most common polar group found in the outer leaflet of the plasma membrane bilayer. Brain ischemia-reperfusion causes lipid peroxidation triggering multiple cell death pathways involving necrosis and apoptosis. Membrane breakdown is, therefore, a major pathophysiologic event in brain ischemia. The ability to achieve membrane repair is a critical step for survival of ischemic neurons following reperfusion injury. The availability of choline is a rate-limiting factor in phospholipid synthesis and, therefore, may be important for timely membrane repair and cell survival. This work aimed at verifying the effects of 7-day oral administration with different doses of choline on survival of CA1 hippocampal neurons following transient global forebrain ischemia in rats. The administration of 400 mg/kg/day divided into two daily doses for 7 consecutive days significantly improved CA1 pyramidal cell survival, indicating that the local availability of this essential nutrient may limit postischemic neuronal survival.

Spatial normalization discrepancies between native and MNI152 brain template scans in gamma ventral capsulotomy patients.

In neurosurgery, spatial normalization emerged as a tool to minimize inter-subject variability and study target point locations based on standard coordinates. The Montreal Neurological Institute's 152 brain template (MNI152) has become the most widely utilized in neuroimaging studies, but has been noted to introduce partial volume effects, distortions, and increase structure size in all directions (x/y/z axes). These discrepancies question the accuracy of the MNI template, as well as its utility for studies that examine and form conclusions from group-level data. Given that surgical precision in obsessive-compulsive disorder is essential to patient outcomes, we retrospectively investigated lesion size and location in patients (n = 21) who underwent capsulotomy for intractable OCD, comparing deviations in the native scans to those in standard space. MNI measurements were significantly larger than native measurements across several structures in both coronal and axial slices, and we found that MNI transformation increases the size of many subcortical structures in a significant and proportional way for both females and males. These findings urge caution when using MNI as a reference space, as well as a stronger consideration of population-specific brain templates when examining connectivity-based networks.

Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part I: pharmacological treatment.

OBJECTIVES: To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD). METHODS: The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). RESULTS: We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD. CONCLUSION: SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed.

Brazilian research consortium on obsessive-compulsive spectrum disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part II: Cognitive-Behavior Therapy treatment.

OBJECTIVE: To summarize the evidence-based cognitive-behavioral therapy (CBT) treatment and propose clinical interventions for adult patients with obsessive-compulsive disorder (OCD). METHODS: A systematic review of the literature on CBT interventions for the treatment of adult OCD, comprising behavior therapy and exposure and response prevention (ERP) was done. The objective of this study is to present updated clinical guidelines to clinicians, providing comprehensive details regarding the necessary procedures to be incorporated into the CBT protocol. We searched the literature published from 2013-2020 in five databases (PubMed, Cochrane, Embase, Psycinfo and Lilacs), considering: study design, primary outcome measures, type of publication and language. Selected articles were assessed for quality with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). RESULTS: We examined 44 new studies used to update the APA guidelines from 2013. High-quality evidence supports CBT including ERP techniques as the first-line CBT treatment for OCD. In addition, protocols for internet-delivered CBT have also demonstrated their efficacy for the treatment of adults with OCD. CONCLUSION: CBT based on ERP is a widely used treatment according to high-quality scientific evidence to treat adults with OCD.

Neurocircuitry of Deep Brain Stimulation for Obsessive-Compulsive Disorder as Revealed by Tractography: A Systematic Review.

Objective: Deep brain stimulation (DBS) was proposed in 1999 to treat refractory obsessive-compulsive disorder (OCD). Despite the accumulated experience over more than two decades, 30-40% of patients fail to respond to this procedure. One potential reason to explain why some patients do not improve in the postoperative period is that DBS might not have engaged structural therapeutic networks that are crucial to a favorable outcome in non-responders. This article reviews magnetic resonance imaging diffusion studies (DTI-MRI), analyzing neural networks likely modulated by DBS in OCD patients and their corresponding clinical outcome. Methods: We used a systematic review process to search for studies published from 2005 to 2020 in six electronic databases. Search terms included obsessive-compulsive disorder, deep brain stimulation, diffusion-weighted imaging, diffusion tensor imaging, diffusion tractography, tractography, connectome, diffusion analyses, and white matter. No restriction was made concerning the surgical target, DTI-MRI technique and the method of data processing. Results: Eight studies published in the last 15 years were fully assessed. Most of them used 3 Tesla DTI-MRI, and different methods of data acquisition and processing. There was no consensus on potential structures and networks underlying DBS effects. Most studies stimulated the ventral anterior limb of the internal capsule (ALIC)/nucleus accumbens. However, the contribution of different white matter pathways that run through the ALIC for the effects of DBS remains elusive. Moreover, the improvement of cognitive and affective symptoms in OCD patients probably relies on electric modulation of distinct networks. Conclusion: Though, tractography is a valuable tool to understand neural circuits, the effects of modulating different fiber tracts in OCD are still unclear. Future advances on image acquisition and data processing and a larger number of studies are still required for the understanding of the role of tractography-based targeting and to clarify the importance of different tracts for the mechanisms of DBS.

Delayed Brain Cyst Formation After Gamma Knife Anterior Capsulotomy.

BACKGROUND: Gamma Knife ventral anterior capsulotomy is an effective option to treat refractory obsessive-compulsive disorder. Although well tolerated, complications can develop years after radiosurgery. We describe a case in which abnormal complications induced by very high doses of radiation evolved. CASE DESCRIPTION: A 55-year-old man with refractory obsessive-compulsive disorder was treated with Gamma Knife ventral anterior capsulotomy using a dose of 180 Gy. His obsessive-compulsive symptoms improved, but his condition evolved with a manic episode, cognitive memory changes, visual hallucinations, confabulation, and frontal lobe symptoms. Magnetic resonance imaging showed brain edema in the left hemisphere and a 6-mm brain cyst in the right hemisphere at postoperative month 20. CONCLUSIONS: This case shows the consequences of affecting more fibers related to the anterior frontal region than intended with a radiosurgical procedure and illustrates the importance of careful clinical and imaging follow-up after Gamma Knife ventral anterior capsulotomy.

Long-term effects for acute phase myocardial infarct VEGF165 gene transfer cardiac extracellular matrix remodeling.

BACKGROUND: Cardiac remodeling is ultimately regulated by components of the extracellular matrix (ECM). We investigated the important role that growth factors play in the regulation of ECM remodeling that occurs as a consequence of myocardium damage. METHODS AND RESULTS: Rats were submitted to the ligation of the left anterior coronary artery and pcDNA3-vascular endothelial growth factor (VEGF)(165) was immediately injected intramyocardially in the treated group. The animals were divided into large size myocardium infarction (LMI) and small size myocardium infarction, with or without gene transfer. The plasmid-containing DNA encoding VEGF(165) was injected into the cardiac muscle and its effect was observed on the ECM components. Glycosaminoglycans were identified and quantified by agarose gel based electrophoresis and ELISA as well as immunocytochemistry to examine specific cathepsin B, heparanase, and syndecan-4 changes. The amounts of hyaluronic acid (HA; p < 0.005), DS, chondroitin sulfate, and heparan sulfate (p < 0.001) were significantly increased in the LMI treated group in comparison to the other groups, which correlates with the decrease in the expression of heparanase. A decrease in the molecular mass of HA was found in the scar tissue of treated group. CONCLUSIONS: The data obtained strongly support the idea that changes in the ECM and its components are important determinants of cardiac remodeling after myocardium infarct and may be essential for inflammatory response and attempt to stabilize the damage and provide a compensatory mechanisms to maintain cardiac output since the ECM components analyzed are involved with angiogenesis, cell proliferation and differentiation.

Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study.

Five refractory obsessive-compulsive patients were assessed using a neuropsychological battery after a modified gamma knife capsulotomy. The surgical technique was not associated with profound cognitive deficits. The authors found improvements in attention, vocabulary, learning, abstract reasoning, and memory.

Treatment of resistant obsessive-compulsive disorder with ventral capsular/ventral striatal gamma capsulotomy: a pilot prospective study.

A subgroup of obsessive-compulsive disorder (OCD) patients remains refractory to conventional treatments. For them, a new stereotactic radiosurgery has been recently developed: the ventral capsular/ventral striatal (VC/VS) gamma capsulotomy. The authors aim to report efficacy and adverse events of VC/VS gamma capsulotomy. Five refractory OCD patients were selected. The authors assessed OCD, anxiety and depressive symptoms, and side effects pre- and postoperatively. Three patients (60%) met response criteria 48 months after surgery. Adverse effects were episodic and transient. Ventral capsular/ventral striatal gamma capsulotomy holds therapeutic promise, with few adverse effects.

Performance of patients with refractory obsessive-compulsive disorder in the Frontal Systems Behavior Scale.

OBJECTIVE: To compare the performance of patients with obsessive-compulsive disorder (OCD) refractory to conventional treatments to healthy controls according to the Frontal Systems Behaviour Scale (FrSBe), comparing the scale scores within each group (Self or Family) and correlating FrSBe with Y-BOCS, DY-BOCS, tic disorder and age of first symptoms. METHOD: Twenty OCD patients and 20 healthy controls were assessed using the FrSBe, a scale designed to evaluate frontal syndromes. RESULTS: The patients had higher scores when compared with the control group (p value < .001) in terms of total score on the scale for both profile forms (Self and Family). In addition, there was a significant difference between the scores reported by the patients and their respective relatives. However, no correlation was observed between the scale and the other variables. CONCLUSIONS: The scale was able to clearly differentiate patients with OCD from healthy controls. This finding suggests that the FrSBe can be used not only in neurologic patients but also in psychiatric cases such as refractory OCD.

An open-label study of subdermal implants of estradiol-only versus subdermal implants of estradiol plus nomegestrol acetate: effects on symptom control, lipid profile and tolerability.

OBJECTIVE: To compare the effects of continuous 17-beta estradiol-only silastic implants with those of continuous 17-beta estradiol plus continuous nomegestrol acetate silastic implants on symptom control, lipid profile and tolerability in postmenopausal women. METHODS: This was an open-label, parallel-group study. Women with and without uterus and no contraindications to hormone therapy (HT) in this study, we consider as HT the replacement of Estrogens-only and Estrogens + Progestogens Therapy, were enrolled. Each subject was assigned to receive four 17-beta estradiol-only silastic implants (women without uterus), or four 17-beta estradiol plus one nomegestrol acetate silastic implant (women with intact uterus), for 1 year. RESULTS: A total of 40 subjects were enrolled and received, the silastic implants of which 40 (100.0%) subjects completed the study (n = 20, estradiol only; n = 20, estradiol plus nomegestrol acetate). The incidence of postmenopausal symptoms decreased significantly. No significant decreases in total cholesterol (1.3%), low-density lipoprotein cholesterol (1.1%), triglycerides (1.2%) and fasting glucose ((1.3%) serum levels were observed in both groups, whereas high-density lipoprotein (HDL) cholesterol increased significantly (2.8%), during the study in both groups. The incidences of adverse events were similar in both treatment groups. CONCLUSIONS: Women treated with 17-beta estradiol-only silastic implants or 17-beta estradiol plus nomegestrol acetate silastic implants showed significant improvement of postmenopausal symptoms, including urogenital and sexual health symptoms and a significant increase in HDL cholesterol and no significant differences in other lipid profiles and tolerability.

Understanding gamma ventral capsulotomy: Potential implications of diffusion tensor image tractography on target selectivity.

BACKGROUND: The role of tractography in gamma ventral capsulotomy (GVC) planning is still unclear. This paper aims to describe the spatial distribution of medial orbitofrontal cortex (OFC) and lateral OFC fibers passing through the anterior limb of the internal capsule (ALIC) and analyze quantitative tractography parameters that differentiate obsessive-compulsive disorder (OCD) individuals from other neurosurgery functional patients (morbid obesity and Parkinson's disease [PD]). METHODS: Twenty patients undergoing functional stereotactic procedures, between 2013 and 2016, were included in this study. OCD patients underwent GVC (single shot 150 Gy and 4-mm collimators). PD and morbid obesity patients were submitted to deep brain stimulation implants. Diffusion tensor image tractography was reconstructed using Brainlab Elements software (Brainlab AG, Munich, Germany). RESULTS: Nine PD, six morbid obesity, and five OCD patients were included with a mean age of 65.4 ± 9.1, 41.0 ± 8.2, and 31.2 ± 5.5, respectively, which are statistically different from each other (P < 0.001). Fourteen patients (70%) were men. A total of 40 cerebral hemispheres were analyzed. Medial OFC fibers are localized more inferior in the ALIC than the lateral OFC fibers in all hemispheres, but the level of intersection and exact topography of fiber bundles are variable among individuals. Both medial and lateral OFC fiber tracts of PD and morbid obesity patients have lower volume than, respectively, medial and lateral counterparts of OCD patients (P < 0.001). CONCLUSIONS: Medial and lateral OFC tract fibers have a general standard distribution in the anterior internal capsule (lateral OFC higher than medial OFC fibers). There are differences between obesity, Parkinson, and OCD patients regarding fiber tract statistics.

Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: a structural MRI pilot prospective study.

OBJECTIVE: The purpose of this study was to investigate regional structural abnormalities in the brains of five patients with refractory obsessive-compulsive disorder (OCD) submitted to gamma ventral capsulotomy. METHODS: We acquired morphometric magnetic resonance imaging (MRI) data before and after 1 year of radiosurgery using a 1.5-T MRI scanner. Images were spatially normalized and segmented using optimized voxel-based morphometry (VBM) methods. Voxelwise statistical comparisons between pre- and post-surgery MRI scans were performed using a general linear model. Findings in regions predicted a priori to show volumetric changes (orbitofrontal cortex, anterior cingulate gyrus, basal ganglia and thalamus) were reported as significant if surpassing a statistical threshold of p<0.001 (uncorrected for multiple comparisons). RESULTS: We detected a significant regional postoperative increase in gray matter volume in the right inferior frontal gyri (Brodmann area 47, BA47) when comparing all patients pre and postoperatively. CONCLUSIONS: Our results support the current theory of frontal-striatal-thalamic-cortical (FSTC) circuitry involvement in OCD pathogenesis. Gamma ventral capsulotomy is associated with neurobiological changes in the inferior orbitofrontal cortex in refractory OCD patients.

Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal carcinoma.

AIM: To propose a quantitative method to detect heparanase-2 (HPA2) and syndecan-1 (Syn-1) using immunohistochemistry in colorectal (colon and rectal) carcinomas compared with nonneoplastic tissues and evaluate the possible role of these molecules in tumor development and extracellular remodeling. METHODS: Cytoplasmic staining of HPA2 and Syn-1 was obtained by standard immunohistochemical reactions in 50 colorectal carcinoma and 20 nonneoplastic large bowels tissues. An image system was used to quantify the immunoexpression by digital computer-assisted method (Matos et al. 2006). The cutoff point for the immunohistochemistry variable was defined by sensibility and specificity curves. Statistical analysis was performed using SPSS version 13.0. RESULTS: HPA2 was over-expressed in colorectal cancer (131.1+/-24.9 o.u./microm) when compared with nonneoplastic tissues (27.9+/-12.2 o.u./microm) (P<0.0001). However, an opposite correlation was observed between Syn-1 and tumor presence, where colorectal tissues expressed lower Syn-1 proteoglycan compared with nonneoplastic tissues, respectively (39.2+/-17.8 o.u./microm) and (102.2+/-25.2 o.u./microm) (P<0.0001). CONCLUSION: A methodology with high sensitivity and specificity is proposed with a cutoff value for HPA2 and Syn-1 in the immunohistochemistry assay to define the presence of tumor. It was demonstrated for the first time in the literature that HPA2 is over-expressed in colorectal carcinoma tissues compared with nonneoplastic tissues. HPA2 over-expression could be possibly related to Syn-1 shedding despite the fact that HPA2 does not present enzymatic activity as HPA1.

Personality traits and treatment outcome in obsessive-compulsive disorder.

OBJECTIVE: Comorbidity with personality disorders in obsessive-compulsive patients has been widely reported. About 40% of obsessive-compulsive patients do not respond to first line treatments. Nevertheless, there are no direct comparisons of personality traits between treatment-responsive and non-responsive patients. This study investigates differences in personality traits based on Cloninger's Temperament and Character Inventory scores between two groups of obsessive-compulsive patients classified according to treatment outcome: responders and non-responders. METHOD: Forty-four responsive and forty-five non-responsive obsessive-compulsive patients were selected. Subjects were considered treatment-responsive (responder group) if, after having received treatment with any conventional therapy, they had presented at least a 40% decrease in the initial Yale-Brown Obsessive Compulsive Scale score, had rated "better" or "much better" on the Clinical Global Impressions scale; and had maintained improvement for at least one year. Non-responders were patients who did not achieve at least a 25% reduction in Yale-Brown Obsessive Compulsive Scale scores and had less than minimal improvement on the Clinical Global Impressions scale after having received treatment with at least three selective serotonin reuptake inhibitors (including clomipramine), and at least 20 hours of cognitive behavioral therapy. Personality traits were assessed using Temperament and Character Inventory. RESULTS: Non-responders scored lower in self-directedness and showed a trend to score higher in persistence than responders did. CONCLUSION: This study suggests that personality traits, especially self-directedness, are associated with poor treatment response in obsessive-compulsive patients.

Stress in nurses working in intensive care units.

The present study aimed to identify the presence of stress in nurses working in intensive care units, the stressing agents and symptoms associated to the nurses' perceptions of stress, and to assess the correlation between the occurrence of stress, sources of stress, and symptoms shown by the nurses. Seventy-five nurses took part in the study. The data were collected from questionnaires, analyzed with the Pearson correlation coefficients, and adjusted by general linear models. The study showed the presence of stress related to work dissatisfaction, activities regarded as critical situations in intensive care units, symptoms related to cardiovascular, digestive and musculoskeletal disorders. The conclusion is that stress is present in nurses' activities in intensive care units, related to characteristics of the health area itself, causing dissatisfaction and stress-related symptoms.

Assessment of Safety and Outcome of Lateral Hypothalamic Deep Brain Stimulation for Obesity in a Small Series of Patients With Prader-Willi Syndrome.

Importance: Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat. Objective: To test the safety and study the outcome of DBS in patients with PWS. Design, Setting, and Participants: This case series was conducted in the Hospital das Clínicas, University of São Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included. Exposure: Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months). Main Outcomes and Measures: Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits. Results: Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking. Conclusions and Relevance: Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.

Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part II: cognitive-behavioral therapy

Objectives: To summarize evidence-based cognitive-behavioral therapy (CBT) treatment and propose clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The literature on CBT interventions for adult OCD, including BT and exposure and response prevention, was systematically reviewed to develop updated clinical guidelines for clinicians, providing comprehensive details about the necessary procedures for the CBT protocol. We searched the literature from 2013-2020 in five databases (PubMed, Cochrane, Embase, PsycINFO, and Lilacs) regarding study design, primary outcome measures, publication type, and language. Selected articles were assessed for quality with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association. Results: We examined 44 new studies used to update the 2013 American Psychiatric Association guidelines. High-quality evidence supports CBT with exposure and response prevention techniques as a first-line treatment for OCD. Protocols for Internet-delivered CBT have also proven efficacious for adults with OCD. Conclusion: High-quality scientific evidence supports the use of CBT with exposure and response prevention to treat adults with OCD.

Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part I: pharmacological treatment

Objectives: To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). Results: We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD. Conclusion: SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed.

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.