Comorbid major depression in obsessive-compulsive disorder patients

Although major depressive disorder (MDD) has been consistently considered the most frequent complication of obsessive-compulsive disorder (OCD), little is known about the clinical characteristics of patients with both disorders. This study assessed 815 Brazilian OCD patients using a comprehensive psychiatric evaluation. Clinical and demographic variables, including OCD symptom dimensions, were compared among OCD patients with and without MDD. Our findings showed that prevalence rates of current MDD (32%) and lifetime MDD (67.5%) were similar for both sexes in this study. In addition, patients with comorbid MDD had higher severity scores of OCD symptoms. There was no preferential association of MDD with any particular OCD symptom dimension. This study supports the notion that depressed OCD patients present more severe general psychopathology. © 2011 Elsevier Inc. All rights reserved.

Dimensional correlates of poor insight in obsessive-compulsive disorder

Background: Cross-sectional studies have associated poor insight in patients with obsessive-compulsive disorder (OCD) with increased OCD symptom severity, earlier age of onset, comorbid depression, and treatment response. The goal of this current study was to examine the relationship between dimensions of OCD symptomatology and insight in a large clinical cohort of Brazilian patients with OCD. We hypothesized that poor insight would be associated with total symptom severity as well as with hoarding symptoms severity, specifically. Methods: 824 outpatients underwent a detailed clinical assessment for OCD, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS), the Brown Assessment of Beliefs Scale (BABS), a socio-demographic questionnaire, and the Structured Clinical Interview for axis I DSM-IV disorders (SCID-P). Tobit regression models were used to examine the association between level of insight and clinical variables of interest. Results: Increased severity of current and worst-ever hoarding symptoms and higher rate of unemployment were associated with poor insight in OCD after controlling for current OCD severity, age and gender. Poor insight was also correlated with increased severity of current OCD symptoms. Conclusion: Hoarding and overall OCD severity were significantly but weakly associated with level of insight in OCD patients. Further studies should examine insight as a moderator and mediator of treatment response in OCD in both behavioral therapy and pharmacological trials. Behavioral techniques aimed at enhancing insight may be potentially beneficial in OCD, especially among patients with hoarding. © 2011.

Towards a post-traumatic subtype of obsessive-compulsive disorder

We evaluated whether traumatic events are associated with a distinctive pattern of socio-demographic and clinical features of obsessive-compulsive disorder (OCD). We compared socio-demographic and clinical features of 106 patients developing OCD after post-traumatic stress disorder (PTSD; termed post-traumatic OCD), 41 patients developing OCD before PTSD (pre-traumatic OCD), and 810 OCD patients without any history of PTSD (non-traumatic OCD) using multinomial logistic regression analysis. A later age at onset of OCD, self-mutilation disorder, history of suicide plans, panic disorder with agoraphobia, and compulsive buying disorder were independently related to post-traumatic OCD. In contrast, earlier age at OCD onset, alcohol-related disorders, contamination-washing symptoms, and self-mutilation disorder were all independently associated with pre-traumatic OCD. In addition, patients with post-traumatic OCD without a previous history of obsessive-compulsive symptoms (OCS) showed lower educational levels, greater rates of contamination-washing symptoms, and more severe miscellaneous symptoms as compared to post-traumatic OCD patients with a history of OCS. © 2011 Elsevier Ltd.

The acylpolyamines from spider venoms

Acylpolyamines are low molecular mass toxins occurring exclusively in the venoms from solitary wasps and some groups of spiders. Their chemical structures have been elucidated using hyphenated techniques of mass spectrometry, such as LC-MS and MS/MS, or through direct analysis with different types of NMR analyses. The chemical structures of the acylpolyamine toxins from the venoms of Nephilinae orb-web spiders appear to be organized into four parts based on the combinatorial way that the chemical building blocks are bound to each other. An aromatic moiety (part I) is connected through a linker amino acid (part II) to a polyamine chain (part III), which in turn may be connected to an optional tail (part IV). The polyamine chains were classified into seven subtypes according to the different combinations of chemical building blocks. These polyamine chains, in turn, are connected to one of three chromophore moieties: a 2,4-dihydroxyphenyl acetyl group, a 4-hydroxyindolyl acetyl group, or an indolyl acetyl group. They may be connected through an asparagine residue or sometimes through the dipeptide ornithyl asparagine. Also, nine different types of backbone tails may be attached to the polyamine chains. These toxins are noncompetitive blockers of ionotropic glutamate receptors with neuroprotective action against the neuronal death and antiepileptic effect. Thus, compounds of this class of spider venom toxin seem to represent interesting molecular models for the development of novel neuropharmaceutical drugs. © 2012 Elsevier B.V. All rights reserved.

Impulsive compulsivity in obsessive-compulsive disorder: A phenotypic marker of patients with poor clinical outcome

Although traditionally obsessive-compulsive disorder (OCD) and impulse control disorders (ICD) have represented opposing ends of a continuum, recent research has demonstrated a frequent co-occurrence of impulsive and compulsive behaviours, which may contribute to a worse clinical picture of some psychiatric disorders. We hypothesize that individuals with 'impulsive' OCD as characterized by poor insight, low resistance, and reduced control towards their compulsions will have a deteriorative course, greater severity of hoarding and/or symmetry/ordering symptoms, and comorbid ICD and/or substance use disorders (SUD). The sample consisted of 869 individuals with a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Of these, 65 had poor insight, low resistance, and reduced control towards compulsions ('poor IRC') and 444 had preserved insight, greater resistance and better control over compulsions ('good IRC'). These two groups were compared on a number of clinical and demographic variables. Individuals with poor IRC were significantly more likely to have a deteriorative course (p < 0.001), longer duration of obsessions (p = 0.017), greater severity of symmetry/ordering (p < 0.001), contamination/cleaning (p < 0.001) and hoarding (p = 0.002) symptoms, and comorbid intermittent explosive disorder (p = 0.026), trichotillomania (p = 0.014) and compulsive buying (p = 0.040). Regression analysis revealed that duration of obsessions (p = 0.037) and hoarding severity (p = 0.005) were significant predictors of poor IRC. In the absence of specific measures for impulsivity in OCD, the study highlights the utility of simple measures such as insight, resistance and control over compulsions as a phenotypic marker of a subgroup of OCD with impulsive features demonstrating poor clinical outcome. © 2012 Elsevier Ltd.

An exploratory dimensional approach to premenstrual manifestation of obsessive-compulsive disorder symptoms: A multicentre study

Objective: In women with obsessive-compulsive disorder (OCD), symptom severity appears to fluctuate over the course of the menstrual cycle. The objective of this paper was to compare female OCD patients with and without premenstrual worsening of obsessive-compulsive symptoms (OCS), in terms of the clinical characteristics of OCD. Methods: This was a cross-sectional study involving 455 women with OCD, of whom 226 (49.7%) had experienced premenstrual OCS worsening and 229 (50.3%) had not (PMOCS-worse and PMOCS-same groups, respectively). Data were collected with the original and dimensional versions of the Yale-Brown Obsessive-Compulsive Scale, as well as with the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Results: We found significant differences between the PMOCS-same and PMOCS-worse groups, the latter showing a higher frequency of suicidal ideation (P<.001), suicide attempts (P=.027), current use of selective serotonin reuptake inhibitors (P=.022), lifetime use of mood stabilisers (P=.015), and sexual/religious obsessions (P<.001; OR. =1.90), as well as higher scores on the BDI (P<.001) and BAI (P<.001). Conclusion: Underscoring the fact that OCD is a heterogeneous disorder, there appears to be a subgroup of female OCD patients in whom the premenstrual period is associated with a higher frequency of sexual/religious obsessions, depression, anxiety, and suicidality. This might be attributable to hormonal fluctuations. Further studies are warranted in order to investigate this hypothesis by evaluating such patients at different phases of the menstrual cycle, as well as measuring hormonal levels. © 2012 Elsevier Inc.

Differential phosphorylation, desensitization, and internalization of α1A-adrenoceptors activated by norepinephrine and oxymetazoline

Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that a1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the a1B and a1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent a1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that thisproperty of OXY is not limited to recombinant receptors expressed in cell systems. The results of the present study are clearly indicative of agonist-directed a1A-AR regulation. OXY shows functional selectivity relative to NE and PE at a1A-ARs, leading to significant receptor desensitization and internalization, which is important in view of the therapeutic vasoconstrictor effects of this drug and the varied biologic process regulated by α1A-ARs. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.

Clinicopathological significance of ERCC1 expression in breast cancer

The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy in different types of cancer. The aim of the present study was to evaluate the clinicopathological significance of ERCC1 expression in breast cancer patients. We analyzed the immunohistochemical expression of ERCC1 in a tissue microarray from 135 primary breast carcinomas and correlated the immunohistochemical findings with clinicopathological factors and outcome data. ERCC1 expression analysis was available for 109 cases. In this group, 58 (53.2%) were positive for ERCC1. ERCC1-positive expression was correlated with smaller tumor size (P=0.007) and with positivity for estrogen receptor (P=0.040), but no correlation was found with other clinicopathological features. Although not statistically significant, triple negative breast cancers were more frequently negative for ERCC1 (61.5% of the cases) compared to the non-triple negative breast cancer cases (41.5%). In conclusion, ERCC1 expression correlated significantly with favorable prognostic factors, such as smaller tumor size and ER-positivity, suggesting a possible role for ERCC1 as a predictive and/or prognostic marker in breast cancer. © 2013 Elsevier GmbH.

Symptom dimensions are associated with age of onset and clinical course of obsessive-compulsive disorder

Meta-analysis of the heterogeneous symptoms of obsessive-compulsive disorder (OCD) has found a four-factor structure of symptom dimensions consisting of cleaning, forbidden thoughts, symmetry, and hoarding. Research into age of onset of symptom dimensions has yielded inconsistent results, and it is unknown whether symptoms along these dimensions differ in their clinical course. We assessed age of onset and clinical course of different OCD symptom dimensions in a large cohort of adult patients. Nine-hundred fifty-five subjects were assessed using the Dimensional Yale-Brown Obsessive-Compulsive Scale. For age of onset analysis, we tested across three methods of classification: (1) primary (more severe) symptom dimension (2) clinically significant symptoms within a dimension or (3) any symptoms within a dimension. Age of onset was defined as the earliest age of onset reported for any individual item within a symptom dimension. For analysis of different types of clinical course, we used chi-square tests to assess for differences between primary symptom dimensions. OCD symptoms in the symmetry dimension had an earlier age of onset than other OCD symptom dimensions. These findings remained significant across all three methods of classification and controlling for gender and comorbid tics. No significant differences were found between the other dimensions. Subjects with primary OCD symptoms in the forbidden thoughts dimension were more likely to report a waxing-and-waning course, whereas symmetry symptoms were less likely to be associated with a waxing-and-waning course. © 2013.

MyD88 or TRAM knockdown regulates interleukin (IL)-6, IL-8, and CXCL12 mRNA expression in human gingival and periodontal ligament fibroblasts

Background: In a previous report, it was shown that Toll-like receptor (TLR) 2 knockdown modulates interleukin (IL)-6 and IL-8 but not the chemokine CXCL12, an important mediator with inflammatory and proangiogenic effects, in human gingival fibroblasts (HGF) and human periodontal ligament fibroblasts (HPDLF). This study investigates whether knocking down two important TLR adaptor molecules, such as myeloid differentiation protein 88 (MyD88) and TRIF-related adaptor molecule (TRAM), could affect mRNA expression of IL-6, IL-8, and CXCL12 in HGF and HPDLF. Methods: After small interfering (si) RNA-mediated silencing of MyD88 or TRAM, HGF and HPDLF were stimulated with Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) or two synthetic ligands of TLR2 (Pam2CSK4 and Pam3CSK4) for 6 hours. IL-6, IL-8, and CXCL12 mRNAs were evaluated by quantitative polymerase chain reaction. Results: Knockdown of MyD88 or TRAM partially impaired the IL-8 mRNA upregulation in both fibroblast subpopulations. Similarly, IL-6 upregulation was partially prevented by siMyD88 or siTRAM in HGF stimulated with Pg LPS, as well as in both fibroblast subtypes challenged with Pam2CSK4. Conversely, constitutive CXCL12 mRNA levels were upregulated by MyD88 or TRAM knockdown in non-stimulated cells. Conclusions: These results suggest that TLR adaptor molecules knockdown, such as MyD88 or TRAM, can decrease IL-6 and IL-8 mRNA and increase CXCL12 mRNA expression in HGF and HPDLF. This can be an important step for better understanding the mechanisms that control the inflammatory cytokine and chemokine expression, which in turn contributes to periodontal pathogenesis.

The systematic significance of floral morphology, nectaries, and nectar concentration in epiphytic cacti of tribes Hylocereeae and Rhipsalideae (Cactaceae)

A long-standing interest in cactus taxonomy has existed since the Linnaean generation, but an appreciation of the reproductive biology of cacti started early in the 1900s. Numerous studies indicate that plant reproductive traits provide valuable systematic information. Despite the extensive reproductive versatility and specializations in breeding systems coupled with the striking floral shapes, the reproductive biology of the Cactaceae has been investigated in approximately 10% of its species. Hence, the systematic value of architectural design and organization of internal floral parts has remained virtually unexplored in the family. This study represents the most extensive survey of flower and nectary morphology in the Cactaceae focusing on tribes Hylocereeae and Rhipsalideae (subfamily Cactoideae). Our objectives were (1) to conduct comparative morphological analyses of flowers and floral nectaries and (2) to compare nectar solute concentration in these two tribes consisting of holo- and semi-epiphytic species. Flower morphology, nectary types, and sugar concentration of nectar have strong taxonomic implications at the tribal, generic and specific levels. Foremost, three types of nectaries were found, namely chamber nectary (with the open and diffuse subtypes), furrow nectary (including the holder nectary subtype), and annular nectary. All Hylocereeae species possess chamber nectaries, in which the nectarial tissue has both trichomes and stomata. The Rhipsalideae are distinguished by two kinds of floral nectaries: furrow and annular, both nectary types with stomata only. The annular nectary type characterizes the genus Rhipsalis. Nectar concentration is another significant taxonomic indicator separating the Hylocereeae and Rhipsalideae and establishing trends linked to nectar sugar concentration and amount of nectar production in relation to flower size. There is an inverse relationship between flower size and amount of nectar production in the smaller Rhipsalideae flowers, in which nectar concentration is more than two-fold higher despite the smaller volume of nectar produced when compared to the large Hylocereeae flowers. Variability of nectary morphology and nectar concentration was also evaluated as potential synapomorphic characters in recent phylogenies of these tribes. In conclusion, our data provide strong evidence of the systematic value of floral nectaries and nectar sugar concentration in the Cactaceae, particularly at different taxonomic levels in the Hylocereeae and Rhipsalideae. © 2013 Perspectives in Plant Ecology, Evolution and Systematics.

Symptom dimensions, clinical course and comorbidity in men and women with obsessive-compulsive disorder

The study aimed to compare male and female patients with obsessive-compulsive disorder (OCD) across symptom dimensions, clinical course and comorbidity. A cross-sectional study was undertaken with 858 adult OCD patients (DSM-IV) from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. Patients were evaluated using structured interviews, including the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) and the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). The sample was composed of 504 women (58.7%) and 354 men (41.3%) with a mean age of 35.4 years-old (range: 18-77). Men were younger, more frequently single and presented more tics, social phobia and alcohol use disorders. Among men, symptom interference occurred earlier and symptoms of the sexual/religious dimension were more common and more severe. Conversely, women were more likely to present symptoms of the aggressive, contamination/cleaning and hoarding dimension and comorbidity with specific phobias, anorexia nervosa, bulimia, trichotillomania, skin picking and compulsive buying. In the logistic regression, female gender remained independently associated with the aggressive and contamination/cleaning dimensions. In both genders the aggressive dimension remained associated with comorbid post-traumatic stress disorder, the sexual/religious dimension with major depression and the hoarding dimension with tic disorders. Gender seems to be relevant in the determination of OCD clinical presentation and course and should be considered an important aspect when defining more homogeneous OCD subgroups. © 2012 Elsevier B.V.

Clinical features of pure obsessive-compulsive disorder

Objective Psychiatric comorbidity is the rule in obsessive-compulsive disorder (OCD); however, very few studies have evaluated the clinical characteristics of patients with no co-occurring disorders (non-comorbid or pure OCD). The aim of this study was to estimate the prevalence of pure cases in a large multicenter sample of OCD patients and compare the sociodemographic and clinical characteristics of individuals with and without any lifetime axis I comorbidity. Method A cross-sectional study with 955 adult patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Assessment instruments included the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, The USP-Sensory Phenomena Scale and the Brown Assessment of Beliefs Scale. Comorbidities were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders. Bivariate analyses were followed by logistic regression. Results Only 74 patients (7.7%) presented pure OCD. Compared with those presenting at least one lifetime comorbidity (881, 92.3%), non-comorbid patients were more likely to be female and to be working, reported less traumatic experiences and presented lower scores in the Y-BOCS obsession subscale and in total DY-BOCS scores. All symptom dimensions except contamination-cleaning and hoarding were less severe in non-comorbid patients. They also presented less severe depression and anxiety, lower suicidality and less previous treatments. In the logistic regression, the following variables predicted pure OCD: sex, severity of depressive and anxious symptoms, previous suicidal thoughts and psychotherapy. Conclusions Pure OCD patients were the minority in this large sample and were characterized by female sex, less severe depressive and anxious symptoms, less suicidal thoughts and less use of psychotherapy as a treatment modality. The implications of these findings for clinical practice are discussed. © 2013 Elsevier Inc. All rights reserved.

Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological markers in cancer is a useful tool to determine patient prognosis. Ki--67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki--67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki--67 and local recurrence in STSs. The use of Ki--67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression.

Triplet entropy analysis of hemagglutinin and neuraminidase sequences measures influenza virus phylodynamics

The influenza virus has been a challenge to science due to its ability to withstand new environmental conditions. Taking into account the development of virus sequence databases, computational approaches can be helpful to understand virus behavior over time. Furthermore, they can suggest new directions to deal with influenza. This work presents triplet entropy analysis as a potential phylodynamic tool to quantify nucleotide organization of viral sequences. The application of this measure to segments of hemagglutinin (HA) and neuraminidase (NA) of H1N1 and H3N2 virus subtypes has shown some variability effects along timeline, inferring about virus evolution. Sequences were divided by year and compared for virus subtype (H1N1 and H3N2). The nonparametric Mann-Whitney test was used for comparison between groups. Results show that differentiation in entropy precedes differentiation in GC content for both groups. Considering the HA fragment, both triplet entropy as well as GC concentration show intersection in 2009, year of the recent pandemic. Some conclusions about possible flu evolutionary lines were drawn. © 2013 Elsevier B.V.