N-Acetyl Cysteine (NAC) in the treatment of obsessive-compulsive disorder: a 16-week, double-blind, randomised, placebo-controlled study

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. The amino acid-based nutraceutical N-acetyl cysteine (NAC) is a safe and readily available agent that has been found to modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. OBJECTIVE: The aim of this study was to assess the efficacy and safety of NAC in treating OCD. METHODS: A 16-week, double-blind, placebo-controlled, randomised trial using 3 g/day of NAC (1.5 g twice daily) in 44 participants (aged 18-70 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-diagnosed OCD, during 2013-2015. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS), conducted every 4 weeks. RESULTS: Analysis of the full sample (intention-to-treat) with repeated measures mixed linear modelling revealed a nonsignificant time × treatment interaction for the YBOCS scale total score (p = 0.39). A per-protocol analysis removing protocol violators also failed to show a significant time × treatment interaction for YBOCS total score (p = 0.15). However, a significant time × treatment interaction was observed for the YBOCS 'Compulsions' subscale in favour of NAC (p = 0.013), with a significant reduction observed at week 12 (dissipating at week 16). At 16 weeks, only four (20 %) participants were considered 'responders' (YBOCS ≥35 % reduction at endpoint) versus four (27 %) in the placebo group. The NAC was well-tolerated, aside from more cases of heartburn occurring compared with placebo (p = 0.045). CONCLUSION: Further research involving NAC for OCD may require larger samples to detect moderate or small effect sizes, involve dosage or formulation differences, use in concert with exposure therapy, or an additional post-study observational period to mitigate study withdrawal. TRIAL REGISTRATION: ACTRN12613000310763.

Fear of self and unacceptable thoughts in obsessive-compulsive disorder

Cognitive-behavioural models have linked unacceptable or repugnant thoughts in obsessive-compulsive disorder (OCD) with vulnerable self-themes and fear-of-self concerns. To investigate this notion, Aardema and coworkers recently developed and validated the Fear of Self-Questionnaire (FSQ) in non-clinical samples, finding it had 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 and inferential confusion). The current article describes two studies that aim to replicate and extend these findings in clinical OCD and non-clinical samples. Study 1 investigated the psychometric properties of an Italian translation of the FSQ in a non-clinical sample (n=405). Results of confirmatory factor analysis supported the unidimensionality of the scale; the FSQ also showed very good internal consistency and temporal stability. Study 2 investigated the role of fear of self in OCD symptoms, and unacceptable thoughts and repugnant obsessions in particular, using a clinical OCD sample (n=76). As expected, fear of self was a unique, major predictor of unacceptable thoughts independent of negative mood states and obsessive beliefs. Moreover, even when considered with obsessive beliefs, anxiety and depression, the feared self was the only unique predictor of obsessionality, providing support for the notion that self-themes could explain why some intrusions convert into obsessions, whereas others do not. Implications for current cognitive-behavioural models are discussed.

Relationship obsessive-compulsive disorder: interference, symptoms, and maladaptive beliefs

BACKGROUND: Obsessive preoccupation, doubts, and compulsive behaviors focusing on one's romantic relationship and partner are receiving increasing clinical, theoretical, and empirical attention. Commonly referred to as relationship obsessive-compulsive disorder (ROCD), such symptoms have been linked with decreased relational and sexual functioning and lower mood, even after controlling for other obsessive-compulsive disorder (OCD) symptoms. To date, however, these symptoms have been studied in community samples alone. In the present study, we compared levels of interference, OCD, and mood symptoms between clinical participants with ROCD, OCD, and community controls. We also examined group differences in maladaptive beliefs previously linked with OCD and ROCD.

METHOD: Participants included 22 ROCD clients, 22 OCD clients, and 28 community controls. The Mini International Neuropsychiatric Interview was used to attain clinical diagnoses of OCD and ROCD. The Yale-Brown Obsessive-Compulsive Scale was used to evaluate primary-symptoms severity. All participants completed measures of symptoms and dysfunctional beliefs.

RESULTS: ROCD clients reported more severe ROCD symptoms than the OCD and control groups. ROCD and OCD clients did not differ in severity of their -primary-symptoms. ROCD clients scored higher than the other groups on maladaptive OCD-related and relationship-related beliefs. Finally, ROCD clients showed more severe depression symptoms than community controls.

CONCLUSION: ROCD is a disabling presentation of OCD that warrants research attention. Maladaptive OCD-related and relationship-related beliefs may be implicated in the development and maintenance of ROCD.

Cultural issues in understanding and treating obsessive compulsive and spectrum disorders

This chapter discusses the cross-cultural understanding of the obsessive compulsive and spectrum disorders. Epidemiological studies suggest a reasonably consistent prevalence of OCD around the world. The role of other culturally influenced factors in the presentation of OCD is also considered (i.e., religiosity, superstition, and beliefs), with religion considered particularly important in the presentation of OCD, although not in its prevalence per se. Treatment effect sizes across countries and within minority cultures from Western countries are outlined. The influence of cultural factors on help-seeking behaviors, assessment, misdiagnosis, and treatment are considered. Limitations of the literature base are discussed, particularly the lack of non-Western studies of treatment effects, and the low evidence base for the spectrum disorders.

Desire for control, sense of control and obsessive-compulsive symptoms

While 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. In this article it was hypothesized that OCD symptoms may be linked with a higher desire to control (DC), but a lower sense of control (SC) over the self and environment, leading to motivation for compulsive symptoms. This hypothesis was investigated in an analogue population, using regression analyses controlling for depression and anxiety. Consistent with predictions, it was found that higher levels of DC and lower levels of SC were associated with higher levels of OCD-related beliefs and symptoms. While control cognitions were linked with the OCD-related beliefs of perfectionism and the over-estimation of threat, they did not relate to cognitions concerning the importance of/need to control thoughts. With respect to specific OCD-symptoms, control cognitions were most strongly related to contamination obsessions/washing compulsions. Implications for theory and treatment 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.

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.

N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review

Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area.

Validation of the Italian version of the Yale-Brown Obsessive Compulsive Scale-Second Edition (Y-BOCS-II) in a clinical sample

OBJECTIVE: The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the most widely accepted measure of obsessive-compulsive disorder (OCD) symptom severity. Recently, the scale has been revised into a second edition (Y-BOCS-II) in order to improve its measurement properties. The present study aimed to evaluate the psychometric properties of the Italian version of the Y-BOCS-II Severity Scale (SS) in a large clinical sample. METHOD: The original version of the Y-BOCS-II was translated into Italian, which involved forward and back-translation procedures. The Italian Y-BOCS-II-SS was administered to one hundred twenty-five treatment-seeking adults with OCD, together with the original Y-BOCS-SS and a battery of self-report measures assessing OCD symptom severity and depressive and anxious symptomology. The factor structure, internal consistency, temporal stability, and construct validity were investigated on the whole sample, while inter-rater and test-retest reliability were assessed on a subsample of participants. RESULTS: Factor analyses revealed a two-factor structure different from those of the original scale, comprising (1) symptom severity; and (2) interference from symptoms. Internal consistency, test-retest reliability over a 2-week period and inter-rater reliability were satisfactory. The Y-BOCS-II-SS also showed excellent construct validity (and better than the Y-BOCS-SS), with good convergent and discriminant validity when assessed against other OCD symptom measures and measures of depression, anxiety and worry. CONCLUSIONS: These findings suggest that the Italian version of the Y-BOCS-II-SS retains the adequate psychometric properties of the original and that it can be confidently used as an assessment tool of OCD symptoms in both clinical and research settings.

Fear of self, doubt and obsessive compulsive symptoms

BACKGROUND AND OBJECTIVES: Following observations in the literature that obsessions often contain or imply negative evaluative information about the self, Aardema et al. (2013) recently developed a measure of feared-self relevant to OCD. The current study aimed to provide further examination of the relevance of such feared self-beliefs to obsessive compulsive processes - in particular whether they partially underlie doubt in OCD-relevant situations. METHOD: Nonclinical participants (N = 463; 291 females; Mage = 25.17, SD = 7.47), were presented with three vignettes, related to washing, checking and non-OCD relevant themes, which assessed doubt through providing alternating sensory and possibility-based information. RESULTS: Higher levels of OCD symptoms and feared-self beliefs both significantly predicted both higher baseline levels of doubt and greater fluctuation in levels of doubt in both the contamination and checking scenarios, and to a much lesser extent in the control scenario. Feared-self beliefs did not predict fluctuation in doubt over-and-above OCD symptoms, consistent with a mediation model. LIMITATIONS: The main limitation was the use of a non-clinical sample, although this allowed sufficient participant numbers to test hypotheses. CONCLUSIONS: The findings provided further experimental support for reasoning processes in OCD, and suggested that feared self-beliefs may make individuals vulnerable to experiencing doubt. Additionally, these results suggested that individuals with high OCD symptoms and those with high feared self-beliefs are unable to recognise the improbable nature of possibility-based statements. Implications for treatment and theory are discussed.

Self-based concepts and obsessive-compulsive phenomena

BACKGROUND/AIMS: Using a cognitive framework, this paper examined self-perceptions as a vulnerability to phenomena in obsessive-compulsive disorder. Specifically, Guidano and Liotti's model of self-ambivalence (from 1983) and the notion of self-worth contingent upon moral standards were investigated as possible mechanisms to explain how individuals come to notice their unwanted intrusions. METHOD: Using an analogue framework, participants were first-year undergraduate psychology students (95 females, mean age = 22.49 years, SD = 7.96, and 25 males, mean age = 21.64 years, SD = 7.26) who were administered a battery of self-report questionnaires. RESULTS: Results indicated that self-ambivalence moderated the relationship between high moral standards and obsessive-compulsive (OC) phenomena; individuals who had high moral standards and high self-ambivalence showed increased OC vulnerability. CONCLUSIONS: The findings suggest that ambivalence about moral self-worth may constitute a particular vulnerability to OC symptoms. Directions for future research are discussed and implications of the findings explored.