Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive–compulsive disorder

Brain Structure and Function - Neurobiological models have provided consistent evidence of the involvement of cortical–subcortical circuitry in obsessive–compulsive disorder (OCD). The...     

The obsessive–compulsive spectrum in the perinatal period: a prospective pilot study

This study aims to describe the phenomenology of obsessive–compulsive symptoms (OCS) and disorders (OCD) in perinatal women and to explore the relationship of OCS/OCD to postpartum depression. A prospective longitudinal study of 44 women screened with the Obsessive–Compulsive Inventory—Revised (OCI-R) and Edinburgh Postnatal Depression Scale (EPDS) between 30 and 37 weeks of pregnancy. Twenty-four women completed a diagnostic interview and the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) before delivery and were contacted postpartum to repeat the EPDS and Y-BOCS. In the third trimester, 32% reported high levels of anxiety and/or depressive symptoms (EPDS ≥ 10 and/or OCI-R ≥ 15) and 29% of those who completed the diagnostic interview met criteria for OCD. At 1 month postpartum, 12.5% had new OCS (Y-BOCS ≥ 8) and 25% had new high levels of depressive symptoms (EPDS ≥ 10). OCS increased in intensity postpartum but did not change in character. OCD and OCS may be of greater prevalence during the perinatal period than previously recognized. The high rates provide new information and require replication in larger, more diverse populations. Research in the perinatal period must expand beyond the exploration of depression to include anxiety disorders and specifically OCD.     

Multiple pathways to functional impairment in obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) is a chronic and debilitating condition that is relatively common in both children and adults, and it is associated with a wide range of functional impairments. Mental health researchers and practitioners have placed considerable attention on OCD over the past two decades, with the goal of advancing treatment and understanding its etiology. Until recently, it was unknown to what extent this disorder was associated with functional impairment. However, recent research shows that the condition has significant social and occupational liabilities. This article discusses etiology, common symptom presentations (including comorbid and ancillary symptoms), basic OCD subtypes, neuropsychological functioning, and the relation these have with functional disability in OCD. Recommendations for future research are also considered.     

Disrupted cortical network as a vulnerability marker for obsessive–compulsive disorder

Morphological alterations of brain structure are generally assumed to be involved in the pathophysiology of obsessive–compulsive disorder (OCD). Yet, little is known about the morphological connectivity properties of structural brain networks in OCD or about the heritability of those morphological connectivity properties. To better understand these properties, we conducted a study that defined three different groups: OCD group with 30 subjects, siblings group with 19 subjects, and matched controls group with 30 subjects. A structural brain network was constructed using 68 cortical regions of each subject within their respective group (i.e., one brain network for each group). Both small-worldness and modularity were measured to reflect the morphological connectivity properties of each constructed structural brain network. When compared to the matched controls, the structural brain networks of patients with OCD indeed exhibited atypical small-worldness and modularity. Specifically, small-worldness showed decreased local efficiency, and modularity showed reduced intra-connectivity in Module III (default mode network) and increased interconnectivity between Module I (executive function) and Module II (cognitive control/spatial). Intriguingly, the structured brain networks of the unaffected siblings showed similar small-worldness and modularity as OCD patients. Based on the atypical structural brain networks observed in OCD patients and their unaffected siblings, abnormal small-worldness and modularity may indicate a candidate endophenotype for OCD.     

Neural time course of threat-related attentional bias and interference in panic and obsessive–compulsive disorders

Attentional biases to threat are considered central to anxiety disorders, however physiological evidence of their nature and time course is lacking. Event-related potentials (ERPs) characterized sensory and cognitive changes while 20 outpatients with panic disorder (PD), 20 with obsessive–compulsive disorder (OCD), and 20 healthy controls (HCs) responded to the color (emotional Stroop task) or meaning of threatening and neutral stimuli. ERPs indicated larger P1 amplitude and longer N1 latency in OCD, and shorter P1 latency in PD, to threatening (versus neutral) stimuli, across instructions to attend to, or ignore, threat content. Emotional Stroop interference correlated with phobic anxiety and was significant in PD. Participants with emotional Stroop interference had augmented P1 and P3 amplitudes to threat (versus neutral) stimuli when color-naming. The results suggest early attentional biases to threat in both disorders, with disorder-specific characteristics. ERPs supported preferential early attentional capture and cognitive elaboration hypotheses of emotional Stroop interference.     

Is episodic obsessive compulsive disorder bipolar? A report of four cases

Several reports have noted cases of OCD which were unusual in showing an abrupt remission. We report longitudinal clinical observation of four cases of acute onset OCD without major depression through a variety of treatments. These patients had prominent feelings of shamefulness; compared to patients with typical OCD they were ill for months rather than years and were older. Two had previous episodes of psychiatric illness with full recovery. Full and persistent recovery occurred in response to lithium or an acute course of ECT but not to tricyclic or SSRI antidepressants. The generalizability of these observations is limited by its uncontrolled nature and the small numbers. The courses observed were consistent with episodic OCD as a possible expression of bipolar disorder and consideration of corresponding treatments. This perspective offers a new rationale for reported observations of remissions of acute onset OCD in response to lithium without lithium effectiveness for typical OCD.     

Effects of the active constituents of Crocus Sativus L., crocins,in an animal model of obsessive–compulsive disorder

Crocins are among the active components of the plant Crocus Sativus L. C. Sativus L. and its constituents were effective in different models of psychiatric disorders including anxiety and depression. Obsessive–compulsive disorder (OCD) is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions. The non selective serotonin (5-HT) receptor agonist mCPP is known to induce OCD-like behavior (excessive self-grooming) in rodents and exacerbate symptoms in patients with OCD. The present study investigated whether or not crocins were able to counteract excessive self-grooming induced by mCPP (0.6 mg/kg, i.p.) in rats. Crocins (30 and 50 mg/kg, i.p.) attenuated mCPP-induced excessive self-grooming. The present results also indicate that these effects of crocins on an animal model of OCD cannot be attributed to changes in locomotor activity. Our findings suggest that the active constituents of C. Sativus L. crocins might play a role in compulsive behavior and support a functional interaction between crocins and the serotonergic system.     

Distinct correlates of hoarding and cleaning symptom dimensions in relation to onset of obsessive–compulsive disorder at menarche or the perinatal period

Ninety female outpatients with obsessive–compulsive disorder (OCD) completed a semistructured interview to assess the relationship between different OCD symptom dimensions and the onset of OCD at menarche or during the perinatal period. Patients with hoarding symptoms had an earlier age at menarche than non-hoarders (12.1 ± 1.3 vs 13.0 ± 1.5 years, p = 0.019) and were more likely to report OCD onset at menarche (OR = 4.1, p = 0.034). Patients with symptoms of the contamination/cleaning dimension were more likely to report the onset of their disorder during pregnancy or postpartum (OR = 9.3, p = 0.048).     

Could obsessive–compulsive disorder have originated as a group-selected adaptive trait in traditional societies?

Obsessive-compulsive disorder (OCD) possesses distinctive characteristics inviting evolutionary and anthropological explanations. A genetically based condition with low fecundity persisting through generations is paradoxical. The concept of group selection is an evolutionary principle capable of clarifying the perplexing epidemiology of OCD. Using a group-selection paradigm, the authors propose that OCD reflects an ancient form of behavioural specialization. The majority of compulsions such as checking, washing, counting, needing to confess, hoarding and requiring precision, all carry the potential to benefit society. Focussing primarily on hunting and gathering cultures, the potential evolutionary advantages of OCD are explored.     

Development and validation of the multidimensional version of the fear of self questionnaire: Corrupted,culpable and malformed feared possible selves in obsessive–compulsive and body-dysmorphic symptoms

In recent years, cognitive-behavioural models of OCD have increasingly recognized the potential role of feared possible selves in the development and maintenance of OCD, while simultaneously re-examining factors that have historically been linked to self-perceptions in OCD. The current article describes the development and validation of a multidimensional version of the Fear of Self Questionnaire (FSQ-EV) in a non-clinical (N = 626) and clinical OCD sample (N = 79). Principal component analyses in the non-clinical sample revealed three conceptually and factorially distinct components revolving around a feared corrupted possible self, a feared culpable possible self and a feared malformed possible self. The questionnaire showed a strong internal inconsistency, and good divergent and convergent validity, including strong relationships to obsessional symptoms. In particular, the corrupted feared self predicted OCD symptoms independently from depression and other related self-constructs and obsessive beliefs, while also strongly interacting with importance and control of thoughts in the prediction of almost all specific symptoms of OCD. Results are consistent with the notion that self-constructs can be conceptually and empirically distinguished from obsessive beliefs and appraisals with significant potential to improve our understanding of OCD and related disorders.     

The anticancer efficacy of pixantrone-loaded liposomes decorated with sialic acid–octadecylamine conjugate

Based on the knowledge that sialic acid is a critical element for tumor development and its receptors are highly expressed on the tumor-associated macrophages (TAMs) which play important roles in the growth and metastasis of tumors, we synthesized a sialic acid–octadecylamine conjugate (SA–ODA) and anchored it on the surface of pixantrone (Pix)-loaded liposomes, to achieve an improved anticancer effect. Four Pix formulations (Pix-S, Pix-CL, Pix-PL and Pix-SAL represent solution, conventional liposome, stealth liposome, and SA–ODA modified liposome, respectively) were developed, and various parameters, including drug loading, stability, in vitro release, cytotoxicity and pharmacokinetics, were evaluated. The tumor growth inhibition and toxicity studies were performed in S180-bearing Kunming mice. Pix-S exhibited a strong toxicity to the immune system, accelerated the growth of tumors and reduced the lifespan of mice. In contrast, Pix-SAL displayed the strongest anticancer and life-prolonging effects among all of the formulations in this study. More importantly, injection of Pix-SAL induced a phenomenon whereby the cancerous tissues were “shed” from mice, after which the wound healed. We speculate that this special efficacy may be partly due to the killing of TAMs by Pix-SAL. This study suggests that SA–ODA modified liposomes may serve as an effective intravenous delivery vehicle for Pix.     

Obsessive–compulsive disorder and gut microbiota dysregulation

Obsessive–compulsive disorder (OCD) is a debilitating disorder for which the cause is not known and treatment options are modestly beneficial. A hypothesis is presented wherein the root cause of OCD is proposed to be a dysfunction of the gut microbiome constituency resulting in a susceptibility to obsessional thinking. Both stress and antibiotics are proposed as mechanisms by which gut microbiota are altered preceding the onset of OCD symptomology. In this light, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) leading to episodic OCD is explained not by group A beta-hemolytic streptococcal infections, but rather by prophylactic antibiotics that are administered as treatment. Further, stressful life events known to trigger OCD, such as pregnancy, are recast to show the possibility of altering gut microbiota prior to onset of OCD symptoms. Suggested treatment for OCD would be the directed, specie-specific (re)introduction of beneficial bacteria modifying the gut microbiome, thereby ameliorating OCD symptoms. Special considerations should be contemplated when considering efficacy of treatment, particularly the unhealthy coping strategies often observed in patients with chronic OCD that may need addressing in conjunction with microbiome remediation.     

The reduction of anti-cancer drug antagonism by the spatial protection of drugs with PLA–TPGS nanoparticles

Docetaxel (DCL) and tamoxifen (TAM) individually are potent drugs in the fight against breast cancer. However when used in combination, they become antagonistic because of differential metabolism of both drugs. We reasoned that by spatially protecting them from metabolizing enzymes with poly (lactide)-d-α-tocopheryl polyethylene glycol succinate (PLA–TPGS) nanoparticles (NPs), we might reduce this drug antagonism. We now report that the drug antagonism between DCL and TAM in MCF7 cell line, was significantly reduced when co-delivered in PLA–TPGS NPs. In addition, this effect of NPs attenuated at high drug concentrations. To investigate the role of NPs in the reduction of drug antagonism, we quantified cellular uptake of the fluorescent model drug coumarin 6 (C6) encapsulated in a rigorous permutation of drugs-nanoparticles ratios. NPs carrying C6 exhibited enhanced cellular uptake over their free C6 counterparts at correspondingly low drug concentrations. This led us to conclude that the reduction of drug antagonism by NPs is correlated to cellular uptake and being in NPs therefore protects both drugs until they are released intracellular for therapeutic anti-cancer effect.     

The Cross-Generational Mother–Daughter–Aunt–Niece Design: Establishing Validity of the MDAN Design with NLSY Fertility Variables

Using National Longitudinal Survey of Youth (NLSY) fertility variables, we introduce and illustrate a new genetically-informative design. First, we develop a kinship linking algorithm, using the NLSY79 and the NLSY-Children data to link mothers to daughters and aunts to nieces. Then we construct mother–daughter correlations to compare to aunt–niece correlations, an MDAN design, within the context of the quantitative genetic model. The results of our empirical illustration, which uses DF Analysis and generalized estimation equations (GEE) to estimate biometrical parameters from NLSY79 sister–sister pairs and their children in the NLSY-Children dataset, provide both face validity and concurrent validity in support of the efficacy of the design. We describe extensions of the MDAN design. Compared to the typical within-generational design used in most behavior genetic research, the cross-generational feature of this design has certain advantages and interesting features. In particular, we note that the equal environment assumption of the traditional biometrical model shifts in the context of a cross-generational design. These shifts raise questions and provide motivation for future research using the MDAN and other cross-generational designs. Edited by Danielle Dick.     

Bloodstream infection with extended-spectrum beta-lactamase–producing Escherichia coli: The role of virulence genes

BackgroundExtraintestinal pathogenic Escherichia coli (ExPEC) strains hold the responsibility for the majority of E. coli infections. Numerous extraintestinal virulence factors (VFs) were possessed by ExPEC which are involved in the pathogenesis of infection. However, the effect of comorbidities or infection syndrome in the association of VFs and mortality remains inconclusive.MethodThis study addressed whether specific sequence type (ST) and VFs of extended-spectrum beta-lactamase–producing E. coli (ESBL-EC) are associated with different outcomes in patients with bloodstream infection. 121 adults from southern Taiwan with ESBL-EC bloodstream infections were enrolled during a 6-year period. Demographic data, including infection syndromes, underlying disease and outcomes, were collected. The virulence factors in isolates were analyzed by PCR and multilocus sequence typing analyses were also performed.ResultPositivity for the virulence genes iha, hlyD, sat, iutA, fyuA, malX, ompT, and traT was associated with ST131 positivity (P < 0.05). Some ESBL-EC virulence genes associated with urinary tract infection (UTI) were revealed. Positivity for ST405 and the virulence genes iroN and iss were significantly associated with increased 30-day mortality (death within 30 days) on univariate analysis (P < 0.05). Independent risk factors of 30-day mortality in bacteremic patients with UTI included underlying chronic liver disease and malignancy. ST131 was borderline associated with 30-day mortality. Independent risk factors associated with 30-day mortality among bacteremic patients without UTI included comorbidities and iroN positivity.ConclusionIn bacteremic patients with UTI, and the ST131 clone was borderline associated with mortality. Positivity for the virulence gene iroN may be linked to mortality in bacteremic patients without UTI.