Mindfulness-based cognitive therapy neurobiology in treatment-resistant obsessive-compulsive disorder: A domain-related resting-state networks approach.

Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes -the precuneus and the frontopolar cortex- were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.

Inflammation in obsessive-compulsive disorder: A literature review and hypothesis-based potential of transcranial photobiomodulation.

Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder that affects about 2%-3% of the global population. Despite the availability of several treatments, many patients with OCD do not respond adequately, highlighting the need for new therapeutic approaches. Recent studies have associated various inflammatory processes with the pathogenesis of OCD, including alterations in peripheral immune cells, alterations in cytokine levels, and neuroinflammation. These findings suggest that inflammation could be a promising target for intervention. Transcranial photobiomodulation (t-PBM) with near-infrared light is a noninvasive neuromodulation technique that has shown potential for several neuropsychiatric disorders. However, its efficacy in OCD remains to be fully explored. This study aimed to review the literature on inflammation in OCD, detailing associations with T-cell populations, monocytes, NLRP3 inflammasome components, microglial activation, and elevated proinflammatory cytokines such as TNF-α, CRP, IL-1ß, and IL-6. We also examined the hypothesis-based potential of t-PBM in targeting these inflammatory pathways of OCD, focusing on mechanisms such as modulation of oxidative stress, regulation of immune cell function, reduction of proinflammatory cytokine levels, deactivation of neurotoxic microglia, and upregulation of BDNF gene expression. Our review suggests that t-PBM could be a promising, noninvasive intervention for OCD, with the potential to modulate underlying inflammatory processes. Future research should focus on randomized clinical trials to assess t-PBM's efficacy and optimal treatment parameters in OCD. Biomarker analyses and neuroimaging studies will be important in understanding the relationship between inflammatory modulation and OCD symptom improvement following t-PBM sessions.

Pallidum volume as a predictor for the effectiveness of mindfulness-based cognitive therapy and psycho-education in unmedicated patients with obsessive-compulsive disorder.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) has been documented to be effective in treating obsessive-compulsive disorder (OCD). However, the neurobiological basis of MBCT remains largely elusive, which makes it clinically challenging to predict which patients are more likely to respond poorly. Hence, identifying biomarkers for predicting treatment outcomes holds both scientific and clinical values. This prognostic study aims to investigate whether pre-treatment brain morphological metrics can predict the effectiveness of MBCT, compared with psycho-education (PE) as an active placebo, among patients with OCD. METHODS: A total of 32 patients with OCD were included in this prognostic study. They received magnetic resonance imaging (MRI) brain scans before treatment. Subsequently, 16 patients received 10 weeks of MBCT, while the other 16 patients underwent a 10-week PE program. The effectiveness of the treatments was primarily assessed by the reduction rate of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score before and after the treatment. We investigated whether several predefined OCD-associated brain morphological metrics, selected based on prior published studies by the ENIGMA Consortium, could predict the treatment effectiveness. RESULTS: Both the MBCT and PE groups exhibited substantial reductions in Y-BOCS scores over 10 weeks of treatment, with the MBCT group showing a larger reduction. Notably, the pallidum total volume was associated with treatment effectiveness, irrespective of the intervention group. Specifically, a linear regression model utilizing the pre-treatment pallidum volume to predict the treatment effectiveness suggested that a one-cubic-centimeter increase in pallidum volume corresponded to a 22.3% decrease in the Y-BOCS total score reduction rate. CONCLUSIONS: Pallidum volume may serve as a promising predictor for the effectiveness of MBCT and PE, and perhaps, other treatments with the shared mechanisms by MBCT and PE, among patients with OCD.

The promise and challenges of transcranial magnetic stimulation and deep brain stimulation as therapeutic options for obsessive-compulsive disorder.

INTRODUCTION: Obsessive compulsive disorder (OCD) represents a complex and often difficult to treat disorder. Pharmacological and psychotherapeutic interventions are often associated with sub-optimal outcomes, and 40-60% of patients are resistant to first line therapies and thus left with few treatment options. OCD is underpinned by aberrant neurocircuitry within cortical, striatal, and thalamic brain networks. Considering the neurocircuitry impairments that underlie OCD symptomology, neurostimulation therapies provide an opportunity to modulate psychopathology in a personalized manner. Also, by probing pathological neural networks, enhanced understanding of disease states can be obtained. AREAS COVERED: This perspective discusses the clinical efficacy of TMS and DBS therapies, treatment access options, and considerations and challenges in managing patients. Recent scientific progress is discussed, with a focus on neurocircuitry and biopsychosocial aspects. Translational recommendations and suggestions for future research are provided. EXPERT OPINION: There is robust evidence to support TMS and DBS as an efficacious therapy for treatment resistant OCD patients supported by an excellent safety profile and favorable health economic data. Despite a great need for alternative therapies for chronic and severe OCD patients, resistance toward neurostimulation therapies from regulatory bodies and the psychiatric community remains. The authors contend for greater access to TMS and DBS for treatment resistant OCD patients at specialized sites with appropriate clinical resources, particularly considering adjunct and follow-up care. Also, connectome targeting has shown robust predictive ability of symptom improvements and holds potential in advancing personalized neurostimulation therapies.

Neural mechanisms of acceptance-commitment therapy for obsessive-compulsive disorder: a resting-state and task-based fMRI study.

BACKGROUND: There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI). METHODS: Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks. RESULTS: Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular-left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure. CONCLUSIONS: These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.

Treatment of disgust in specific emotional disorders.

Although conditioning approaches have highlighted potential characteristics of disgust in anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), these findings have yet to be translated into evidence-based treatments. Examination of the literature suggests various indicators of disgust that predict treatment outcome in these disorders. However, mechanisms remain unclear because studies examining disgust during the course of treatment are limited. Increasingly, the field has moved toward experimental investigation of strategies that reduce disgust. While cognitive reappraisal and imagery techniques appear promising, such techniques have yet to be examined as anxiety disorder treatments in large-scale randomized clinical trials. The literature also points to novel approaches to treating disgust, ranging from an inhibitory-informed approach to exposure therapy to transcranial direct current stimulation. However, the development of novel treatment approaches will require more rigorous experimental psychopathology approaches that can further elucidate processes that contribute to the etiology and/or maintenance of disorders of disgust.

Obsessive-compulsive existential type: a dialectical-phenomenological approach.

The clinical presentation of obsessive-compulsive patients is characterized by unwanted, intrusive, nonsensical, self-related, and recurrent ideas, thoughts, images, or impulses associated with active compulsive compensations. Under the operational diagnostic criteria adopted by the biological- and cognitive-oriented neopositivist medical paradigm, it is known as "obsessive-compulsive disorder." However, this paradigm has been criticized for its controversial assumptions, limited methodologies, theoretic biases, and inconsistency in producing practical outcomes. To bypass some of these issues, we propose a complementary approach that draws on and further develops existing psychopathological studies of the obsessive-compulsive anthropological condition based on dialectical phenomenological psychopathology. As such, we refer to the global clinical configuration as the "obsessive-compulsive existential type." Our theoretical inspiration comes from the classical phenomenological work on obsessions undertaken by Straus and Gebsattel, which identified the negative transformation of the obsessive-compulsive life-world or the endogenous emergence of the anti-eidos (diluting existential force). We then propose to broaden the concept of anti-eidos, especially in its dialectical correlation with eidos (unifying existential force), representing the existential dialectic between transformation and permanence. Next, we detail the dynamics of anthropological disproportions in obsessive-compulsive existential type, essentially the supremacy of the anti-eidos over the eidos. This primary imbalance modifies the obsessive-compulsive existential structure, consisting of polymorphic temporality; weakened intentionality; maladjusted calibration of distance with the world and others; an integral, isolated, besieged self with dwindling self-agency, and tense and over-protecting embodiment. We also analyze compensatory hyperreflexivity and compulsive rituals as expressions of structural counterbalancing designed to contain the primary structural disproportions and derangements. The heterogeneous obsessive-compulsive clinical manifestations are the complex result of the primary structural alteration and subsequent phenomenological compensations. They tend to be variable in temporal span and rarely assume a fixed form, hindering diagnosis. We correlate structural frameworks with multiple clinical examples. Finally, we raise some insights on how our study may contribute to scientific research and therapeutic proposals.

Neurofeedback for obsessive compulsive disorder: A randomized, double-blind trial.

We aim to develop fMRI neurofeedback as a treatment for obsessive compulsive disorder (OCD). In prior work, we found that providing neurofeedback of activity in the anterior prefrontal cortex (aPFC) improved control over contamination anxiety in a subclinical population. Here, we present the results of a randomized, double-blind clinical trial (NCT02206945) testing this intervention in patients with OCD. We recruited patients with primary symptoms in the fear-of-harm/checking or contamination/washing domains. During neurofeedback, they viewed symptom provocative images and attempted to up- and down-regulate the aPFC during different blocks of time. The active group received two sessions of neurofeedback and the control group received yoked sham feedback. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Symptom scale. The secondary outcome was control over aPFC. Thirty-six participants completed feedback training (18 active, 18 control). The active group had a slightly but significantly greater reduction of obsessive-compulsive symptoms after neurofeedback compared to the control group (p<.05) but no significant differences in control over the aPFC. These data demonstrate that neurofeedback targeting the aPFC can reduce symptoms in OCD. Future investigations should seek to optimize the training protocol to yield larger effects and to clarify the mechanism of action.

Microbial Reprogramming in Obsessive-Compulsive Disorders: A Review of Gut-Brain Communication and Emerging Evidence.

Obsessive-compulsive disorder (OCD) is a debilitating mental health disorder characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Dysbiosis, an imbalance in the gut microbial composition, has been associated with various health conditions, including mental health disorders, autism, and inflammatory diseases. While the exact mechanisms underlying OCD remain unclear, this review presents a growing body of evidence suggesting a potential link between dysbiosis and the multifaceted etiology of OCD, interacting with genetic, neurobiological, immunological, and environmental factors. This review highlights the emerging evidence implicating the gut microbiota in the pathophysiology of OCD and its potential as a target for novel therapeutic approaches. We propose a model that positions dysbiosis as the central unifying element in the neurochemical, immunological, genetic, and environmental factors leading to OCD. The potential and challenges of microbial reprogramming strategies, such as probiotics and fecal transplants in OCD therapeutics, are discussed. This review raises awareness of the importance of adopting a holistic approach that considers the interplay between the gut and the brain to develop interventions that account for the multifaceted nature of OCD and contribute to the advancement of more personalized approaches.

Adverse events in cognitive behavioral therapy and relaxation training for children and adolescents with obsessive-compulsive disorder: A mixed methods study and analysis plan for the TECTO trial.

Background: Knowledge on adverse events in psychotherapy for youth with OCD is sparse. No official guidelines exist for defining or monitoring adverse events in psychotherapy. Recent recommendations call for more qualitative and quantitative assessment of adverse events in psychotherapy trials. This mixed methods study aims to expand knowledge on adverse events in psychotherapy for youth with OCD. Methods: This is an analysis plan for a convergent mixed methods study within a randomized clinical trial (the TECTO trial). We include at least 128 youth aged 8-17 years with obsessive-compulsive disorder (OCD). Participants are randomized to either family-based cognitive behavioral therapy (FCBT) or family-based psychoeducation and relaxation training (FPRT). Adverse events are monitored quantitatively with the Negative Effects Questionnaire. Furthermore, we assess psychiatric symptoms, global functioning, quality of life, and family factors to investigate predictors for adverse events. We conduct semi-structured qualitative interviews with all youths and their parents on their experience of adverse events in FCBT or FPRT. For the mixed methods analysis, we will merge 1) a qualitative content analysis with descriptive statistics comparing the types, frequencies, and severity of adverse events; 2) a qualitative content analysis of the perceived causes for adverse events with prediction models for adverse events; and 3) a thematic analysis of the participants' treatment evaluation with a correlational analysis of adverse events and OCD severity. Discussion: The in-depth mixed methods analysis can inform 1) safer and more effective psychotherapy for OCD; 2) instruments and guidelines for monitoring adverse events; and 3) patient information on potential adverse events. The main limitation is risk of missing data. Trial registration: ClinicalTrials.gov identifier: NCT03595098. Registered on July 23, 2018.

Omega-3 as an adjuvant in the treatment eating and psychological symptoms in patients with anorexia nervosa: a systematic review and meta-analyses.

BACKGROUND: This study was carried out to assess the effects of omega-3 supplementation as an adjunct treatment for eating and psychological symptoms in patients with anorexia nervosa. METHODS: We conducted a systematic review of the literature using the terms 'anorexia nervosa' AND 'Fatty Acids, Omega-3'. Five randomised controlled trials with a total of 144 participants, published between 2003 and 2022, were included. RESULTS: The effects of supplementation of omega-3 on anxiety were standardised mean difference (SMD) 0.79, 95% confidence interval (CI) -0.08 to 1.66; p = 0.08; I² = 3%; two studies, 33 participants; moderate quality of evidence. For depression, the supplementation of omega-3 was SMD: 0.22, 95% CI: -0.50 to 0.93; p = 0.18; I² = 45%; two studies, 33 participants; moderate quality of evidence. For obsessive-compulsive disorder, the supplementation of omega-3 was SMD: -0.22, 95% CI: -0.70 to 2.25; p = 0.36; I² = 0%; three studies, 32 participants; low quality of evidence. CONCLUSION: This research showed that regardless of dose, time or, if associated with other components, the use of omega-3 supplementations as an adjuvant treatment showed no evidence of effect in eating and psychological symptoms in patients with anorexia nervosa.

Association between obsessive-compulsive disorder and the risk of schizophrenia using the Korean National Health Insurance Service-National Sample Cohort: a retrospective cohort study.

AIMS: Obsessive-compulsive disorder (OCD) and schizophrenia are often reported as co-morbid conditions. However, the evidence of an association between OCD and the risk of schizophrenia is limited. This study investigated the risk of schizophrenia in patients newly diagnosed with OCD using a nationally representative sample cohort in South Korea. METHODS: Data were obtained from the 2002-2013 Korean National Health Insurance Service-National Sample Cohort of the National Health Insurance Service. Using propensity score matching, 2509 patients with OCD and a control group of 7527 patients were included in the analysis. Chi-squared tests were used to investigate and compare the general characteristics of the study population. The risk of schizophrenia was analysed using the Cox proportional hazard model. RESULTS: The incidence rate was 45.79/10 000 person-year for patients with OCD and 4.19/10 000 person-year for patients without OCD. Patients with OCD had a higher risk of schizophrenia compared to the control group after adjusting for covariates (hazard ratio = 10.46, 95% confidence interval = 6.07-18.00). CONCLUSIONS: This study identified an association between the diagnosis of OCD and the risk of schizophrenia in a South Korean national representative cohort. Further research using a prospective design to clarify the causality of OCD in schizophrenia in a controlled environment should be conducted to validate these findings.

Cyclic versus continuous deep brain stimulation in patients with obsessive compulsive disorder: A randomized controlled trial.

BACKGROUND: Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is effective for refractory obsessive-compulsive disorder (OCD), but patients typically require high stimulation voltages and DBS comes with a risk for adverse events (AE). OBJECTIVE: The aim of the present study was to advance DBS for OCD by optimizing energy efficiency and minimize adverse events using a cyclic form of stimulation METHODS: This double blind, randomized crossover trial compares 2 weeks of continuous versus cyclic DBS (0.1 s ON, 0.2 s OFF) in 16 patients with OCD. We compared OCD symptoms (Yale-Brown Obsessive-Compulsive Scale, Y-BOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), AEs, battery life, cognitive performance and quality of life. RESULTS: Average Y-BOCS scores at baseline increased significantly with 5.5 points (p = 0.006) in the cyclic condition. Average HAM-D and HAM-A scores increased with 2.2 (p = 0.088) and 2.8 points (p = 0.018). The overall health scale of quality of life worsened during cyclic DBS (p = 0.044). Patients reported on average 3.3 AEs during continuous stimulation and 4.4 AEs during cyclic stimulation (p = 0.175), though stimulation-related AEs such as headache and concentration problems reduced during cyclic DBS. Battery usage during continuous DBS was 0.021 V per hour compared to 0.008 V per hour during cyclic DBS. CONCLUSION: Though specific stimulation-related AEs improved, cyclic stimulation (0.1 s ON, 0.2 s OFF) comes with a high relapse risk in patients with DBS for OCD. Cyclic DBS is no alternative for standard DBS treatment, but applicable in case of debilitating AEs.

Glutamatergic neurotransmission is affected by low-frequency repetitive transcranial magnetic stimulation over the supplemental motor cortex of patients with obsessive-compulsive disorder.

OBJECTIVE: In obsessive-compulsive disorder (OCD), glutamatergic neurotransmission dysfunction played key roles in pathophysiology. The current research assessed changes of neurometabolites in the bilateral striatum of OCD patients receiving low-frequency repetitive transcranial magnetic stimulation (rTMS) using 1H proton magnetic resonance spectroscopy (1H-MRS). METHODS: 52 OCD patients were divided into rTMS treatment group (29) and the control group (medication only) (22). The levels of neurometabolites in the bilateral striatum of patients with OCD were measured using MRS before and after treatment. All participants were taking medication prior to the treatment and the process. RESULTS: Following rTMS treatment, Yale-Brown Obsessive-Compulsive Scale (YBOCS) score was significantly decreased in the rTMS group compared with the control group. Glutamate (Glu) and glutamate and glutamine complexes (Glx) in the bilateral striatum of the rTMS treatment response group increased significantly with the improvement of OCD. Glu in the bilateral striatum and Glx in the right striatum were positively correlated with compulsion after the treatment. CONCLUSIONS: The physiopathological mechanism of OCD may be related to the glutamatergic dysfunction, and the low-frequency repetitive transcranial magnetic stimulation applied to the supplementary motor area can improve OCD symptoms by modulating glutamatergic levels in the bilateral striatum of patients with OCD.

Effectiveness of adjunctive low-frequency repetitive transcranial magnetic stimulation therapy over the left dorsolateral prefrontal cortex in patients with obsessive-compulsive disorder refractory to medical treatment:A double-blind, randomized clinical trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common psychiatric disorder. The Food and Drug Administration (FDA) approved repetitive transcranial magnetic stimulation (rTMS) to treat OCD in 2018. So far, various approaches to treat this disorder have been evaluated. We evaluated the effect of adjunctive low-frequency rtMS over the left dorsolateral prefrontal cortex in patients with OCD refractory to treatment. METHODS: The present clinical trial was done on 37 patients with OCD referring from the psychiatry clinic, 22 Bahman Hospital, Qazvin province, between 2018 and 2020 and patients were randomly divided into two groups. The intervention group received rTMS treatment at 1 Hz for 20 min (1200 pulses/day) over the left DLPFC area as adjunctive to the medical treatment three times a week and for five weeks, whereas those in the control group were subjected to only the sham condition plus their medical treatment. The Yale-Brown Obsessive-Compulsive Scale (Y-BOC.S) was completed by patients before the study, following sessions 5 and 10 during the intervention, at the end of the intervention, and three to six months after the intervention under the direct supervision of a psychiatrist. SPSS software version 26 was used to compare the results between the two groups. RESULTS: The intervention group showed significantly lower mean Y-BOCS scores after the intervention and at follow-up (P < 0.05) and all patients of the intervention group showed significantly lower Y-BOCS scores than their own baseline scores (P < 0.05). Also, using antipsychotic agents along with the serotonergic agents yielded significantly lower scores in the intervention group at the end of the intervention (P < 0.05). All the patients were found with higher follow-up scores than their scores at the end of the intervention; however, this difference was not significant (p > 0.05). CONCLUSION: Adjunctive low-frequency (1 Hz) rTMS over the left DLPFC is able to effectively reduce Y-BOCS score in OCD patients refractory to treatment following 15 sessions, and the reduction was durable even after three to six months. Using antipsychotic agents as an adjuvant with serotonergic agents was identified as a possible predictor for response to adjunctive rTMS therapy.

Decreased vitamin D levels in obsessive-compulsive disorder patients.

OBJECTIVE: The present paper compared vitamin D levels in adult patients with obsessive-compulsive disorder (OCD) and explored possible correlations with patients' characteristics. METHODS: Fifty outpatients with OCD, according to DSM-5 criteria, were included and assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HRDS). RESULTS: All the patients except one showed lower vitamin D levels than normative values (>30 nm/L). Vitamin D values of the whole sample were negatively correlated with Y-BOCS total, compulsion subscale, and some items' scores, specifically "interference from obsessions," "distress associated with obsessions," and "time spent on compulsions". The same relationships were detected in men, while women showed negative correlations between vitamin D levels and Y-BOCS compulsion subscale and "resistance to compulsions," "degree of control of compulsions," "insight" item scores. CONCLUSIONS: Our findings would indicate that vitamin D might be involved in the pathophysiology of OCD, and that it is possibly related to the severity of the disorder and to typical symptoms, with some sex-related peculiarities. Further studies are necessary to support or not our findings and to ascertain the effectiveness of vitamin D supplementation in patients with OCD.

"N-Acetylcysteine for Obsessive-Compulsive and Related Disorders in Children and Adolescents: A Review".

OBJECTIVE: To evaluate clinical data using oral n-acetylcysteine (NAC) in obsessive-compulsive and related disorders (OCDRD) treatment. DATA SOURCES: PubMed, Ovid MEDLINE (1946-July 2022), and the Cochrane Library database were searched using the terms NAC, children, adolescent, obsessive-compulsive disorder (OCD), trichotillomania (TTM), excoriation, hoarding disorder, and body dysmorphic disorder. Bibliographies were reviewed for relevant trials and case studies. STUDY SELECTION AND DATA EXTRACTION: English language, clinical trials, or case studies analyzing NAC use in patients aged 3 to 21 years old with OCDRD as determined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. DATA SYNTHESIS: Three randomized double-blind placebo-controlled trials of NAC in children and adolescents studied 121 patients with OCDRD. Trials assessed symptom severity from baseline to 10 to 12 weeks of NAC therapy. Two OCD trials identified statistically significant improvements, with only 1 trial demonstrating a clear clinically relevant difference from placebo. One trial in TTM found no difference between the NAC and placebo. Adverse effects were mild and included nausea, blurred vision, fatigue, tremor, and sweats. N-acetylcysteine titrated to 2400 or 2700 mg/day in divided doses was the most studied regimen. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Many OCDRD patients fail to completely respond to first-line treatment with cognitive behavioral therapy (CBT) and/or selective serotonin reuptake inhibitors (SSRIs) leaving practitioners with few additional treatment options. Preliminary efficacy and safety data are presented in this review. CONCLUSIONS: Limited evidence suggests children and adolescents with OCD refractory to SSRIs or CBT may benefit from NAC augmentation.

Therapists' problematic experiences when working with obsessive-compulsive disorder: a qualitative investigation of schema modes, mode cycles, and strategies to return to healthy adult mode.

Introduction: Obsessive-compulsive disorder (OCD) is one of the most challenging pathologies for therapists, being chronic and often characterized by frequent relapses. The therapeutic relationship plays a critical role in the outcome of therapy. The dynamic interaction between therapist and client schema modes determines the quality of the relationship. The objective: of the present qualitative research is to investigate and conceptualize the triggers for therapists when working with OCD clients, the therapists' schema modes that are activated, and the strategies they use to get back into the Healthy Adult mode. Method: Using the in-depth interview technique, we interviewed 15 psychotherapists of various therapeutic orientations. After several demographic items, the therapists answered some introductory questions about their general perceptions of working with this pathology. They were then guided to go through a specific therapeutic situation in imagery that they identified as particularly difficult to manage in the therapeutic relationship. For data analysis, we used the interpretative phenomenological analysis (IPA) method and thematic analysis. Results: For therapists working with clients with OCD, two main categories of triggers have been identified: Perceived resistance to change and Superiority. Two other categories, Client immobilized by conflict and Abusive, emerged from our analysis. Therapists' reactions to triggers were synthesized into mode processes that (1) were not acted on and (2) were displayed in relation with the client. For mode processes that therapists did not explicitly act on, there was triggering of the Vulnerable Child in relationship with a Demanding Parent, followed by various coping modes, depending on the category of trigger, and in the displayed mode, most therapists operated in the Healthy Adult mode. With respect to the process, strategies used by therapists to return to Healthy Adult mode that stood out were: focusing on the process, self-acceptance, self-compassion, and somatic grounding strategies, and focusing on the client's resources.

S-ketamine exerts sex- and dose-dependent anti-compulsive-like effect as monotherapy or in augmentation to fluoxetine.

Since a significant body of studies supports the involvement of glutamatergic neurotransmission in the neurobiology of obsessive-compulsive disorder (OCD). Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist with rapid and sustained antidepressant effect, raises as a potential new anti-OCD drug. Evidence from pre-clinical studies indicates that female mice are more sensitive than male mice to ketamine antidepressant effects. Our group previously showed that S-ketamine, one ketamine enantiomer, induces an acute anti-compulsive effect in male mice. Herein, we investigated this S-ketamine effect in female adult Swiss mice as monotherapy or as an adjuvant to fluoxetine, a selective serotonin reuptake inhibitor (SSRI), compared to male mice. For this purpose, we assessed the S-ketamine anti-compulsive-like effect in the marble-burying (MBT) and nest-building (NBT) tests in adult female Swiss mice. S-ketamine reduced the compulsive-like behaviour of female mice in both animal tests in a dose larger (30 mg/kg) than the effective dose in male Swiss mice (10 mg/kg, Tosta et al., 2019). The association of sub-effective doses of S-ketamine and fluoxetine effectively reduced the marble-burying behaviour of both male and female Swiss mice, although male mice present a better response. The variation of female sex hormones (oestrogen and progesterone), inferred by oestrous cycle and ovariectomy, did not influence S-ketamine's response. In conclusion, we found that female mice are less sensitive to S-ketamine's anti-compulsive-like effect than male mice as monotherapy or adjuvant treatment, but oscillations in female sex hormones concentrations do not seem to explain this difference.