We do not see things as they are, we see them as we are : a multidimensional worldview model of obsessive-compulsive disorder

Cognitive-behavioral models of obsessive-compulsive disorder (OCD) assign a central role to specific beliefs and coping strategies in the development, maintenance and exacerbation of obsessive-compulsive (OC) symptoms. These models also implicate perceptions of self and the world in the development and maintenance of OC phenomena (e.g., overestimation of threat, sociotropy, ambivalent or sensitive sense of self, looming vulnerability), although such self and world domains have not always been emphasized in recent research. Following recent recommendations (Doron & Kyrios, 2005), the present study undertook a multifaceted investigation of self and world perceptions in a nonclinical sample, using a coherent worldview framework (Janoff-Bulman, 1989, 1991). Beliefs regarding the self and the world were found to predict OC symptom severity over and above beliefs outlined in traditional cognitive-behavioral models of OCD. Self and world beliefs were also related to other OC-relevant beliefs. Implications of these findings for theory and treatment of OCD are discussed.

Mediated and direct effects of general control beliefs on obsessive compulsive symptoms

Although control-related cognitions have often been implicated in discussions of obsessive compulsive disorder (OCD), empirical investigations of the relationship between control constructs and OCD symptoms have been relatively limited. This article investigated the hypothesis that OCD symptoms may be linked with a higher desire for control (DC), but a lower sense of control (SC) over the self and environment, leading to motivation for compulsive symptoms. It also investigated whether this effect was direct, or mediated through other OCD-related cognitions. This hypothesis was investigated in a nonclinical population, using path analyses controlling for depression. It was found that higher levels of DC and lower levels of SC were associated with higher levels of OCD-related beliefs, and with symptoms via higher OCD-related beliefs. SC was also directly linked with higher OCD symptoms. Control beliefs regarding both the internal (emotions) and external (threat) environment were related to OCD symptoms. Implications for therapy and research are discussed.

Adult attachment insecurities are related to obsessive compulsive phenomena

Obsessive-compulsive disorder (OCD) is one of the most disabling and highly prevalent anxiety disorders. Cognitive models implicate maladaptive beliefs such as inflated sense of responsibility, perfectionism, importance/control of thoughts in the maintenance of the disorder, but little research has investigated factors that may lead to these beliefs. This paper investigated whether a dysfunctional attachment system may be one such factor, by examining how adult attachment orientations (dimensions of attachment anxiety and avoidance) relate to OCDrelated cognitions, OCD symptoms, and depression. Using structural equation modeling in a student sample (N = 446), the present study found evidence for a mediational model, where attachment dimensions contributed to OCD symptoms via OCD-related cognitions, while controlling for depression. The paper discusses the association between adult attachment orientations and OCD symptoms in the context of current cognitive-behavioral theories of OCD.

Cognitive behavioral treatment of obsessive compulsive disorder : a broader framework

Obsessive Compulsive Disorder (OCD) is rated as a leading cause of disability by the World Health Organization (1996). OCD is a heterogeneous and complex anxiety disorder characterized by the occurrence of repeated and distressing intrusive thoughts, and compulsive actions that are performed in order to lessen distress or prevent the negative outcome associated with the intrusions. Over the last several decades, cognitive behavioral treatments (CBT) of OCD have dramatically improved the prognosis for the disorder. However, a significant proportion of individuals presenting with OCD may still fail to benefit from treatment. In this paper, we present current CBT treatment models of OCD. We then propose several ways of enhancing CBT for OCD by targeting clients' attachment anxiety and dysfunctional self perceptions.

Obsessive compulsive disorder : integration of cognitive-behaviour therapy and clinical psychology care into the primary care context

In primary care, evidence-based psychological treatments for obsessive compulsive disorder (OCD), such as cognitive behaviour therapy (CBT), have not been readily available. We aimed to develop models of care for OCD that account for barriers to access and can be integrated into general practice settings. Multiple methodologies and sources were utilised, including literature reviews, a reference group, focus groups, interviews and questionnaire responses from consumers, psychologists and/or GPs. It was found that there were similarities and some differences among stakeholders in attitudes and knowledge about OCD, and views about treatment and assessment in primary care. Three models of care for patients with OCD were developed and integrated into a treatment program operating through a division of general practice. Participating GPs preferred referral to a specialist clinic, irrespective of participation in an educational program about OCD. Based on these findings, it is suggested that effective integration of specialist CBT treatments for OCD into primary care is possible if the needs and views of all stakeholders are accounted for.

The relationship between neuropsychological performance, cognitive confidence, and obsessive-compulsive phenomena : a pilot study

Drawing on neuropsychological and cognitive-behavioral approaches to Obsessive-Compulsive Disorder (OCD), the present study examined the association between memory performance, cognitive confidence, and OCD phenomena. Forty-six analogue participants completed a series of self-report questionnaires and neuropsychological tasks before and after a manipulation of confidence in memory It was found that cognitive confidence predicts OCD symptoms over and above the influence of depressive symptoms and other OCD-related beliefs. Participants reported higher levels of cognitive confidence following positive feedback on the manipulation task. However, changes in cognitive confidence following the manipulation task were not reflected in neuropsychological performance. Implications for theory and treatment are discussed.

The influence of confidence in memory on checking behaviours

Recent theories of Obsessive Compulsive Disorder have suggested that meta-cognitive beliefs, particular confidence in memory, may relate to the maintenance of symptoms. For example, individuals who worry that their memory is deficient may check in order to ensure that the doors are locked, regardless of their actual memory ability. While studies have related meta-memory beliefs to OCD symptoms, and have found that memory is affected by checking behaviours; to date, no experimental literature has attempted to ascertain whether lowered confidence in memory directly leads to greater checking behaviours. In the current study 46 non-clinical participants completed a battery of questionnaires measuring these constructs, before undertaking a “memory task” designed to manipulate their level of confidence in their memory. The effect of the manipulation on the level of checking on a visuomemory task was subsequently assessed. The questionnaires indicated that cognitive confidence predicted variation in obsessive-compulsive symptoms over-and-above the influence of depressive symptoms and other OCD-related beliefs. However, while confidence in memory was successfully manipulated, the group with increased memory confidence was not found to have lower checking behaviours. Limitations of the study are discussed and directions for further research are suggested.

Adult attachment insecurities are associated with obsessive compulsive disorder

Objectives.  Obsessive compulsive disorder (OCD) is one of the most disabling and highly prevalent anxiety disorders (ADs). Current cognitive models of OCD implicate views about the self and world in the maintenance of the disorder. However, little research has focused on issues that may lead to vulnerability to such views. In particular, a person's attachment insecurities (attachment anxiety, avoidance) may be important risk factors increasing the likelihood of such non-adaptive perceptions (Doron & Kyrios, 2005).

Design.  Participants meeting criteria for OCD were compared with cohorts meeting criteria for other ADs and healthy controls on a range of measures including adult attachment, OC symptoms, cognitions, and mood.

Methods.  Diagnosis of the clinical groups was established using the Anxiety Disorders Interview Schedule for DSM-IV (Brown, Di Nardo, & Barlow, 1994). The clinical relevance of attachment insecurities was ascertained by comparing their prevalence in an OCD sample (N= 30), an ADs sample (N= 20), and a community sample (N= 32). Results.  Attachment anxiety was significantly higher in individuals with OCD, even when controlling for depression.

Conclusions.  Addressing attachment anxiety in individuals presenting with OCD may be important for enhancing therapeutic outcomes. However, findings are based on cross-sectional data that preclude conclusions relating to causal influence.

Fear of self and obsessionality: development and validation of the Fear of Self Questionnaire

Obsessions – particularly those directly relating to causing harm – often contain or imply evaluative dimensions about the self, reflecting a fear as to who the person might be – or might become. Following from research indicating that such beliefs are relevant to OCD, and the wider literature in social psychology regarding ‘feared’ or ‘undesired’ self-guides, the current study describes the development and validation of a new questionnaire—the Fear of Self Questionnaire, in 8- and 20-item versions.

The questionnaire was piloted in two non-clinical samples (n=258; n=292). Exploratory and confirmatory factor analyses supported the unidimensionality of the measure. The questionnaire showed a strong internal inconsistency, and good divergent and convergent validity, including strong relationships to obsessional symptoms and with other processes implicated in cognitive models of OCD (e.g. obsessive beliefs, inferential confusion). Implications are discussed.

Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist

An increase in the concentration of serotonin in the brain has been shown to cause fatigue during exercise in humans and experimental animals. This type of fatigue is referred to as central fatigue and is likely to be mediated by the concentration of serotonin as well as serotonin receptor sensitivity. Serotonin (5-HT) receptor antagonism in humans and experimental animals has been shown to improve endurance performance. A previous report has shown decreased receptor sensitivity in athletes compared to sedentary controls. It is unclear whether this is due to a training adaptation or if individuals are predisposed to enhanced athletic performance due to their inherent decreased receptor sensitivity. The present study investigated changes in 5-HT receptor sensitivity in response to aerobic exercise. Subjects completed 3 × 30 min of stationary cycling at 70% of their peak aerobic power (V̇O2,peak) for 9 weeks. Serotonin receptor sensitivity was assessed indirectly by measuring the neuroendocrine response following administration of a serotonin agonist (buspirone hydrochloride). The neuroendocrine response following administration of a placebo was also investigated in a blind crossover design. A group of sedentary control subjects was also recruited to control for seasonal variations in central receptor sensitivity. The training caused a significant increase in V̇O2,peak (3.1 ± 0.16 to 3.6 ± 0.15 l min−1, P < 0.05) and endurance capacity (93 ± 8 to 168 ± 11 min, P < 0.05), but there was no change (P > 0.05) in the neuroendocrine response in the presence of a serotonin agonist. However, one-quarter of the subjects in the training group demonstrated decreases in receptor sensitivity. These results suggest that despite increases in V̇O2,peak and endurance performance, there was no measurable change in 5-HT receptor sensitivity in the presence of a serotonin agonist. In addition, it is possible that changes in receptor sensitivity may take longer to occur, that the training stimulus used in the present investigation was inadequate and/or that changes occurred in receptor subtypes that were not probed by the agonist used in the present investigation.

Efficacy of using cancer stem cell markers in isolating and characterizing liver cancer stem cells

Recent evidence suggests that a subset of hepatocellular carcinomas (HCCs) are derived from liver cancer stem cells (LCSCs). In order to isolate and characterize LCSCs, reliable markers that are specific to these cells are required. We evaluated the efficacy of a range of cancer stem cell (CSC) markers in isolating and characterizing LCSCs. We show that the most widely used CSC markers are not specific to LCSCs. By western analysis, protein expression of the common markers showed no significant difference between HCC tumor tissues and adjacent non-cancerous liver. Further, isolation of LCSCs from common HCC cell lines using FACScan and microbeads showed no consistent marker expression pattern. We also show that LCSCs have unique subtypes. Immunohistochemistry of HCC tissues showed that different HCCs express unique combinations of LCSC markers. Quantitative real-time polymerase chain reaction analysis showed that LCSCs isolated using different markers in the same HCC phenotype had different expression profiles. Likewise, LCSCs isolated from different HCC phenotypes with the same marker also had unique expression profiles and displayed varying resistance profiles to Sorafenib. Thus, using a range of commonly used CSC markers in HCCs and cell lines, we demonstrate that currently available markers are not specific for LCSCs. LCSCs have unique subtypes that express distinctive combinations of LCSC markers and altered drug resistance profiles, making their identification problematic.

Design of multiligand inhibitors for the swine flu H1N1 neuraminidase binding site

Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1). The binding site for these drugs is well established and they were designed based on computational docking studies. We show here that some common natural products have moderate inhibitory activity for H1N1 neuraminidase under docking studies. Significantly, docking studies using AutoDock for biligand and triligand forms of these compounds (camphor, menthol, and methyl salicylate linked via methylene bridges) indicate that they may bind in combination with high affinity to the H1N1 neuraminidase active site. These results also indicate that chemically linked biligands and triligands of these natural products could provide a new class of drug leads for the prevention and treatment of influenza. This study also highlights the need for a multiligand docking algorithm to understand better the mode of action of natural products, wherein multiple active ingredients are present.

Lactam-stabilized helical analogues of the analgesic μ-Conotoxin KIIIA

μ-Conotoxin KIIIA (μ-KIIIA) blocks mammalian voltage-gated sodium channels (VGSCs) and is a potent analgesic following systemic administration in mice. Previous structure–activity studies of μ-KIIIA identified a helical pharmacophore for VGSC blockade. This suggested a route for designing truncated analogues of μ-KIIIA by incorporating the key residues into an α-helical scaffold. As (i, i+4) lactam bridges constitute a proven approach for stabilizing α-helices, we designed and synthesized six truncated analogues of μ-KIIIA containing single lactam bridges at various locations. The helicity of these lactam analogues was analyzed by NMR spectroscopy, and their activities were tested against mammalian VGSC subtypes NaV1.1 through 1.7. Two of the analogues, Ac-cyclo9/13[Asp9,Lys13]KIIIA7–14 and Ac-cyclo9/13[Lys9,Asp13]KIIIA7–14, displayed μM activity against VGSC subtypes NaV1.2 and NaV1.6; importantly, the subtype selectivity profile for these peptides matched that of μ-KIIIA. Our study highlights structure–activity relationships within these helical mimetics and provides a basis for the design of additional truncated peptides as potential analgesics.

Structure of the analgesic μ-Conotoxin KIIIA and effects on the structure and function of disulfide deletion

μ-Conotoxin μ-KIIIA, from Conus kinoshitai, blocks mammalian neuronal voltage-gated sodium channels (VGSCs) and is a potent analgesic following systemic administration in mice. We have determined its solution structure using NMR spectroscopy. Key residues identified previously as being important for activity against VGSCs (Lys7, Trp8, Arg10, Asp11, His12, and Arg14) all reside on an α-helix with the exception of Arg14. To further probe structure−activity relationships of this toxin against VGSC subtypes, we have characterized the analogue μ-KIIIA[C1A,C9A], in which the Cys residues involved in one of the three disulfides in μ-KIIIA were replaced with Ala. Its structure is quite similar to that of μ-KIIIA, indicating that the Cys1−Cys9 disulfide bond could be removed without any significant distortion of the α-helix bearing the key residues. Consistent with this, μ-KIIIA[C1A,C9A] retained activity against VGSCs, with its rank order of potency being essentially the same as that of μ-KIIIA, namely, NaV1.2 > NaV1.4 > NaV1.7 ≥ NaV1.1 > NaV1.3 > NaV1.5. Kinetics of block were obtained for NaV1.2, NaV1.4, and NaV1.7, and in each case, both kon and koff values of μ-KIIIA[C1A,C9A] were larger than those of μ-KIIIA. Our results show that the key residues for VGSC binding lie mostly on an α-helix and that the first disulfide bond can be removed without significantly affecting the structure of this helix, although the modification accelerates the on and off rates of the peptide against all tested VGSC subtypes. These findings lay the groundwork for the design of minimized peptides and helical mimetics as novel analgesics.

Psychotic-like experiences in a community sample of adolescents: implications for the continuum model of psychosis and prediction of schizophrenia

Studies conducted in community samples suggest that psychotic-like experiences are common in the general population, leading to suggestions that they are either variations of normal personality or are different expressions of underlying vulnerability to psychotic disorder. Different types of psychotic symptoms may exist, some being normal variants and some having implications for mental health and functioning. The aim of the present study was to determine if different subtypes of psychotic-like experiences could be identified in a community sample of adolescents and to investigate if particular subtypes were more likely to be associated with psychosocial difficulties, that is, distress, depression and poor functioning, than other subtypes. Eight hundred and seventy-five Year 10 students from 34 schools participated in a cross-sectional survey that measured psychotic-like experiences using the Community Assessment of Psychic Experiences; depression using the Centre for Epidemiologic Studies Depression Scale; and psychosocial functioning using the Revised Multidimensional Assessment of Functioning Scale. Factor analysis was conducted to identify any subtypes of psychotic experiences. Four subtypes of psychotic-like experiences were identified: Bizarre Experiences, Perceptual Abnormalities, Persecutory Ideas, and Magical Thinking. Intermittent, infrequent psychotic experiences were common, but frequent experiences were not. Bizarre Experiences, Perceptual Abnormalities and Persecutory Ideas were strongly associated with distress, depression and poor functioning. Magical Thinking was only weakly associated with these variables. Overall these findings may suggest that infrequent psychotic-like experiences are unlikely to be a specific risk factor for onset of a psychotic disorder in community samples. Given that the different subtypes had varying associations with current difficulties it is suggested that not all subtypes confer the same risk for onset of psychotic disorder and poor outcome. Bizarre Experiences, Perceptual Abnormalities and Persecutory Ideas may represent expressions of underlying vulnerability to psychotic disorder, but Magical Thinking may be a normal personality variant.