Deep Brain Stimulation for Obsessive-Compulsive Disorder and Depression.

The field of stereotactic neurosurgery developed more than 70 years ago to address a therapy gap for patients with severe psychiatric disorders. In the decades since, it has matured tremendously, benefiting from advances in clinical and basic sciences. Deep brain stimulation (DBS) for severe, treatment-resistant psychiatric disorders is currently poised to transition from a stage of empiricism to one increasingly rooted in scientific discovery. Current drivers of this transition are advances in neuroimaging, but rapidly emerging ones are neurophysiological-as we understand more about the neural basis of these disorders, we will more successfully be able to use interventions such as invasive stimulation to restore dysfunctional circuits to health. Paralleling this transition is a steady increase in the consistency and quality of outcome data. Here, we focus on obsessive-compulsive disorder and depression, two topics that have received the most attention in terms of trial volume and scientific effort.

Midbrain dopamine neurons arbiter OCD-like behavior.

The neurobiological understanding of obsessive-compulsive disorder (OCD) includes dysregulated frontostriatal circuitry and altered monoamine transmission. Repetitive stereotyped behavior (e.g., grooming), a featured symptom in OCD, has been proposed to be associated with perturbed dopamine (DA) signaling. However, the precise brain circuits participating in DA's control over this behavioral phenotype remain elusive. Here, we identified that DA neurons in substantia nigra pars compacta (SNc) orchestrate ventromedial striatum (VMS) microcircuits as well as lateral orbitofrontal cortex (lOFC) during self-grooming behavior. SNc-VMS and SNc-lOFC dopaminergic projections modulate grooming behaviors and striatal microcircuit function differentially. Specifically, the activity of the SNc-VMS pathway promotes grooming via D1 receptors, whereas the activity of the SNc-lOFC pathway suppresses grooming via D2 receptors. SNc DA neuron activity thus controls the OCD-like behaviors via both striatal and cortical projections as dual gating. These results support both pharmacological and brain-stimulation treatments for OCD.

Maximizing translational value in models of compulsive behavior: A commentary on Pickenhan et al. (2024).

In this issue of Cognitive, Affective, and Behavioral Neuroscience, Pickenhan et al. (2024) discuss the need for translational studies to understand features underlying obsessive-compulsive disorder (OCD). They highlight the translational value of the observing-response task (ORT) for modeling functional and maladaptive checking behaviors, a common symptom of OCD.

Cerebrospinal fluid findings in patients with obsessive-compulsive disorder, Tourette syndrome, and PANDAS: A systematic literature review.

BACKGROUND: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are related mental disorders that share genetic, neurobiological, and phenomenological features. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is a neuropsychiatric autoimmune disorder with symptoms of OCD and/or TS associated with streptococcal infections. Therefore, PANDAS represents a strong link between OCD, TS, and autoimmunity. Notably, cerebrospinal fluid (CSF) analyses can provide insight into the central nervous processes in OCD, TS, and PANDAS. METHODS: A systematic literature search according to the PRISMA criteria was conducted to collect all CSF studies in patients with OCD, TS, and PANDAS. The total number of cases and the heterogeneity of the low number of studies were not sufficient for a meta-analysis to provide a high level of evidence. Nevertheless, meta-analytical statistics could be performed for glutamate, 5-hydroxyindoleacetic acid (degradation product of serotonin), homovanillic acid (degradation product of dopamine), 3-methoxy-4-hydroxyphenylglycol (major metabolite of noradrenaline), and corticotropin-releasing hormone (CRH) in OCD. A risk-of-bias assessment was implemented using the Cochrane ROBINS-E tool. RESULTS: Meta-analytical testing identified elevated glutamate levels in the CSF of OCD patients compared with healthy controls, while no significant differences were found in other neurotransmitters or CRH. Single studies detected novel neuronal antibodies in OCD patients and elevated oligoclonal bands in TS patients. For TS and PANDAS groups, there was a dearth of data. Risk of bias assessment indicated a substantial risk of bias in most of the included studies. CONCLUSIONS: This systematic review of available CSF data shows that too few studies are currently available for conclusions with good evidence. The existing data indicates glutamate alterations in OCD and possible immunological abnormalities in OCD and TS. More CSF studies avoiding sources of bias are needed.

Obsessive-compulsive symptoms and brain lesions compatible with multiple sclerosis.

Autoimmune-mediated obsessive-compulsive disorder (OCD) can occur in multiple sclerosis (MS). Here, a well-studied case study of a patient with OCD and MS-compatible diagnostic findings is presented. The 42-year-old female patient had displayed OCD symptoms for 6 years. Magnetic resonance imaging (MRI) identified several periventricular and one brainstem lesion suggestive of demyelination. Cerebrospinal fluid (CSF) analyses detected an increased white blood cell count, intrathecal immunoglobulin (Ig) G and IgM synthesis, CSF-specific oligoclonal bands, and a positive MRZ reaction. Neopterin was increased, but sarcoidosis was excluded. In the absence of neurological attacks and clues for MRI-based dissemination in time, a radiologically isolated syndrome, the pre-disease stage of MS, was diagnosed. Neurotransmitter measurements of CSF detected reduced serotonin levels. In the absence of visible strategic demyelinating lesions within the cortico-striato-thalamo-cortical circuits, OCD symptoms may relate to reduced intrathecal serotonin levels and mild neuroinflammatory processes. Serotonin abnormalities in MS should be studied further, as they could potentially explain the association between neuroinflammation and mental illnesses.

Efficacy and acceptability of cognitive-behavioral therapy and serotonin reuptake inhibitors for pediatric obsessive-compulsive disorder: a network meta-analysis.

BACKGROUND: Cognitive-behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) are recommended treatments for pediatric obsessive-compulsive disorder (OCD), but their relative efficacy and acceptability have not been comprehensively examined. Further, it remains unclear whether the efficacy of in-person CBT is conserved when delivered in other formats, such as over telephone/webcam or as Internet-delivered CBT (ICBT). METHODS: PubMed, PsycINFO, trial registries, and previous systematic reviews were searched for randomized controlled trials (RCTs) comparing CBT (in-person, webcam/telephone-delivered, or ICBT) or SRIs with control conditions or each other. Network meta-analyses were conducted to examine efficacy (post-treatment Children's Yale-Brown Obsessive Compulsive Scale) and acceptability (treatment discontinuation). Confidence in effect estimates was evaluated with CINeMA (Confidence in Network Meta-Analysis). RESULTS: Thirty eligible RCTs and 35 contrasts comprising 2,057 youth with OCD were identified. In-person CBT was significantly more efficacious than ICBT, waitlist, relaxation training, and pill placebo (MD range: 3.95-11.10; CINeMA estimate of confidence: moderate) but did not differ significantly from CBT delivered via webcam/telephone (MD: 0.85 [-2.51, 4.21]; moderate), SRIs (MD: 3.07 [-0.07, 6.20]; low), or the combination of in-person CBT and SRIs (MD: -1.20 [-5.29, 2.91]; low). SRIs were significantly more efficacious than pill placebo (MD: 4.59 [2.70, 6.48]; low) and waitlist (MD: 8.03 [4.24, 11.82]; moderate). No significant differences for acceptability emerged, but confidence in estimates was low. CONCLUSIONS: In-person CBT and SRIs produce clear benefits compared to waitlist and pill placebo and should be integral parts of the clinical management of pediatric OCD, with in-person CBT overall having a stronger evidence base. The combination of in-person CBT and SRIs may be most efficacious, but few studies hinder firm conclusions. The efficacy of CBT appears conserved when delivered via webcam/telephone, while more trials evaluating ICBT are needed.

The natural history of lifetime psychiatric disorders in patients with obsessive-compulsive disorder followed over half a century.

OBJECTIVE: Few long-term studies have examined the life-time prevalence of comorbid psychiatric conditions in patients with obsessive-compulsive disorder (OCD). We therefore studied the frequency of comorbid psychiatric disorders, and their relation to onset and prognosis, in patients with OCD who were followed for almost half a century. METHODS: During 1947-1953, 285 OCD patients were admitted as inpatients to a university hospital in Gothenburg, Sweden. Among those, 251 (88%) accepted a structured comprehensive psychiatric examination in 1954-1956. In 1989-1993, 176 survivors were eligible and 144 (response rate 82%) were re-examined. The same psychiatrist performed both examinations. OCD was diagnosed according to the Schneider criteria, and other mental disorders according to DSM-IV. Mean follow-up since onset was 47 years. RESULTS: The lifetime frequency of depressive disorders was 84.7% (major depression 43.8%), generalized anxiety disorder (GAD) 71.5%, panic anxiety disorder 47.9%, agoraphobia 52.1%, specific phobias 64.6%, social phobia 47.9%, paranoid conditions 40.3% (29.1% paranoid ideation), psychotic disorders 15.3%, alcohol abuse 13.2% (men 39%, women 3%) and substance abuse 17.4%. Specific phobia most often started before OCD, while depression had a varied onset in relation to OCD. Social phobia, agoraphobia, GAD, alcohol and substance abuse, psychotic disorders and paranoid conditions most often started after OCD. Presence of GAD, psychotic disorder and substance abuse worsened prognosis of OCD. CONCLUSION: Comorbid psychiatric conditions are common in OCD patients, and have onset throughout the course. OCD signals vulnerability for other psychiatric conditions, which are important to detect in clinical practice as they negatively affect the outcome.

Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder.

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.

Towards the correlates of stressful life events as precipitants of obsessive-compulsive disorder: a systematic review and metanalysis.

Obsessive-compulsive disorder (OCD) is a prevalent condition with multifactorial etiology involving genetic and environmental factors. The present study aims to summarize the correlates of stressful life events (SLEs) in OCD by reviewing studies comparing OCD associated or not with SLEs before its onset. To do so, a systematic review was performed by searching PubMed, Web of Science, Scopus, and PsycINFO databases for studies published between the database's inception and November 27, 2023. Studies including individuals whose OCD was precipitated or not by SLEs (SLEs OCD and NSLEs OCD, respectively) were assessed. Effect sizes or odds ratios were then calculated to identify the strength of association between SLEs and clinical characteristics, such as gender, age of onset, family history of OCD, severity of OCD symptoms, depressive symptoms, and mood comorbidities among patients with OCD. Out of the 4083 records initially identified, 5 studies met the inclusion criteria and 3 were comparable through a meta-analysis. Notably, the analyses were limited by the small number of studies available in the literature. The meta-analysis demonstrated SLEs OCD to be associated with female gender, later OCD onset, and increased comorbidity rates with mood disorders. Despite the cross-sectional nature of the reviewed studies, women may be more vulnerable to develop a later onset of OCD following SLEs, which may also lead to mood disorders. Caution is needed to avoid prematurely classifying this presentation as a distinct subtype of OCD.

An investigation of the experience of control through the sense of agency in people with obsessive-compulsive disorder: a review and meta-analysis.

The construct of sense of agency (SoA) has proven useful for understanding mechanisms underlying obsessive-compulsive disorder (OCD) phenomenology, especially in explaining the apparent dissociation in OCD between actual and perceived control over one's actions. Paradoxically, people with OCD appear to experience both diminished SoA (feeling unable to control their actions) and inflated SoA (having "magical" control over events). The present review investigated the extent to which the SoA is distorted in OCD, in terms of both implicit (ie, inferred from correlates and outcomes of voluntary actions) and explicit (ie, subjective judgment of one's control over an outcome) measures of SoA. Our search resulted in 15 studies that met the criteria for inclusion in a meta-analysis, where we also examined the potential moderating effects of the type of measure (explicit versus implicit) and of the actual control participants had over the outcome. We found that participants with OCD or with high levels of OCD symptoms show lower implicit measures of SoA and at the same time tend to overestimate their control in situations where they do not actually have it. Together, these findings support the hypothesized dissociation in OCD between actual and perceived control over one's actions.

Polygenetic risk scores and phenotypic constellations of obsessive-compulsive disorder in clozapine-treated schizophrenia.

Obsessive-compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive-compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Participants were divided into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS analyses were performed to evaluate the association between either phenotypic OCD or OCS severity and genotype-predicted predisposition for OCD, SCZ, cross-disorder, and CLZ/norclozapine (NorCLZ) ratio, CLZ metabolism and NorCLZ metabolism. OCS and OCD were frequent comorbidities in our sample of CLZ-treated SCZ individuals, with a prevalence of 39.6% and 27.5%, respectively. Furthermore, the Y-BOCS total score correlated positively with the duration of CLZ treatment in years (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). A significant correlation was found between OCD occurrence and PRS for CLZ metabolism. We found no correlation between OCS severity and PRS for CLZ metabolism. We found no correlation for either OCD or OCS and PRS for OCD, cross-disorder, SCZ, CLZ/NorCLZ ratio or NorCLZ metabolism. Our study was able to replicate previous findings on clinical characteristics of CLZ-treated SCZ individuals. OCS is a frequent comorbidity in this cohort and is correlated with CLZ treatment duration in years and PANSS general psychopathology subscale score. We found a correlation between OCD and PRS for CLZ metabolism, which should be interpreted as incidental for now. Future research is necessary to replicate significant findings and to assess possible genetic predisposition of CLZ-treated individuals with SCZ to OCS/OCD. Limitations attributed to the small sample size or the inclusion of subjects on co-medication must be considered. If the association between OCD and PRS for CLZ metabolism can be replicated, it should be further evaluated if CYP1A2 alteration, respectively lower CLZ plasma level, is relevant for OCD development.

EEG microstate co-specificity in schizophrenia and obsessive-compulsive disorder.

The past 20 years of research on EEG microstates has yielded the hypothesis that the imbalance pattern in the temporal dynamics of microstates C (increased) and D (decreased) is specific to schizophrenia. A similar microstate imbalance has been recently found in obsessive-compulsive disorder (OCD). The aim of the present high-density EEG study was to examine whether this pathological microstate pattern is co-specific to schizophrenia and OCD. We compared microstate temporal dynamics using Bayesian analyses, transition probabilities analyses and the Topographic Electrophysiological State Source-Imaging method for source reconstruction in 24 OCD patients and 28 schizophrenia patients, respectively, free of comorbid psychotic and OCD symptoms, and 27 healthy controls. OCD and schizophrenia patients exhibited the same increased contribution of microstate C, decreased duration and contribution of microstate D and greater D → C transition probabilities, compared with controls. A Bayes factor of 4.424 for the contribution of microstate C, 4.600 and 3.824, respectively, for the duration and contribution of microstate D demonstrated that there was no difference in microstate patterns between the two disorders. Source reconstruction further showed undistinguishable dysregulations between the Salience Network (SN), associated with microstate C, and the Executive Control Network (ECN), associated with microstate D, and between the ECN and cognitive cortico-striato-thalamo-cortical (CSTC) loop in the two disorders. The ECN/CSTC loop dysconnectivity was slightly worsened in schizophrenia. Our findings provide substantial evidence for a common aetiological pathway in schizophrenia and OCD, i.e. microstate co-specificity, and same anomalies in salience and external attention processing, leading to co-expression of symptoms.

Mapping the neuroanatomical heterogeneity of OCD using a framework integrating normative model and non-negative matrix factorization.

Obsessive-compulsive disorder (OCD) is a spectrum disorder with high interindividual heterogeneity. We propose a comprehensible framework integrating normative model and non-negative matrix factorization (NMF) to quantitatively estimate the neuroanatomical heterogeneity of OCD from a dimensional perspective. T1-weighted magnetic resonance images of 98 first-episode untreated patients with OCD and matched healthy controls (HCs, n = 130) were acquired. We derived individualized differences in gray matter morphometry using normative model and parsed them into latent disease factors using NMF. Four robust disease factors were identified. Each patient expressed multiple factors and exhibited a unique factor composition. Factor compositions of patients were significantly correlated with severity of symptom, age of onset, illness duration, and exhibited sex differences, capturing sources of clinical heterogeneity. In addition, the group-level morphological differences obtained with two-sample t test could be quantitatively derived from the identified disease factors, reconciling the group-level and subject-level findings in neuroimaging studies. Finally, we uncovered two distinct subtypes with opposite morphological differences compared with HCs from factor compositions. Our findings suggest that morphological differences of individuals with OCD are the unique combination of distinct neuroanatomical patterns. The proposed framework quantitatively estimating neuroanatomical heterogeneity paves the way for precision medicine in OCD.

Resolving heterogeneity in obsessive-compulsive disorder through individualized differential structural covariance network analysis.

BACKGROUND: The high heterogeneity of obsessive-compulsive disorder (OCD) denies attempts of traditional case-control studies to derive neuroimaging biomarkers indicative of precision diagnosis and treatment. METHODS: To handle the heterogeneity, we uncovered subject-level altered structural covariance by adopting individualized differential structural covariance network (IDSCN) analysis. The IDSCN measures how structural covariance edges in a patient deviated from those in matched healthy controls (HCs) yielding subject-level differential edges. One hundred patients with OCD and 106 HCs were recruited and whose T1-weighted anatomical images were acquired. We obtained individualized differential edges and then clustered patients into subtypes based on these edges. RESULTS: Patients presented tremendously low overlapped altered edges while frequently shared altered edges within subcortical-cerebellum network. Two robust neuroanatomical subtypes were identified. Subtype 1 presented distributed altered edges while subtype 2 presented decreased edges between default mode network and motor network compared with HCs. Altered edges in subtype 1 predicted the total Yale-Brown Obsessive Compulsive Scale score while that in subtype 2 could not. CONCLUSIONS: We depict individualized structural covariance aberrance and identify that altered connections within subcortical-cerebellum network are shared by most patients with OCD. These 2 subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of OCD.

ØCD: protocol for the development and evaluation of a cognitive-behavioral prevention program for obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) imposes significant burdens on individuals, families, and healthcare systems and the COVID-19 pandemic appears to have exacerbated OCD symptoms. Currently, there are no validated prevention programs for OCD, highlighting a critical gap in mental health services. This study aims to develop and validate the first ØCD prevention program, for at-risk adults, utilizing cognitive-behavioral therapy (CBT) and exposure response prevention (ERP) techniques. METHODS: A single-blind, randomized controlled trial comparing the ØCD prevention program to a waitlist control group will be conducted. Participants, at-risk adults (18-65 years) with subclinical OCD symptoms (OCI-R score ≥ 12), will be recruited for the study. The ØCD prevention program compresise of six online group sessions incorporating CBT and ERP techniques over three modules. The primary outcomes are OCD symptom severity (measured by the Obsessive-Compulsive Inventory- revised form; OCI-R), depression symptoms (measured by the Patient Health Questionnaire; PHQ-9), and anxiety symptoms (measured by the Generalised Anxiety Disorder 7-item; GAD-7). Secondary outcomes include OCD-related beliefs, experiential avoidance, resilience, quality of life, uncertainty intolerance, automatic thoughts, and distress. Outcome measures will be collected at baseline, at completion of the intervention, and one year later (follow-up). At follow-up, we will also analyze the OCD diagnostic incidence, using the Structured Clinical Interview for DSM-5. We will employ a multivariate analysis of variance (MANOVA) to explore whether significant differences exist between groups across dependent variables. To compare the OCD incidence levels from the pre-test to the follow-up we will use the chi-squared test. DISCUSION: The present study may contribute novel data on the efficacy of OCD prevention approaches, leading to the development of an evidence-based OCD prevention program that could alleviate individual and societal burdens associated with OCD. TRIAL REGISTRATION: This trial was approved by the University Ethical Review Authority (937/ 28.11.2023) at Babeș-Bolyai University and is registered on clinicaltrials.gov (ID: NCT06262464).

The effectiveness and acceptability of the Bergen 4-day treatment for adolescents with OCD: a replication and extension.

BACKGROUND: B4DT is a concentrated treatment format with prolonged sessions of exposure and ritual prevention (ERP) delivered over four consecutive days. Two previous open trials demonstrated promising results of the Bergen 4-day treatment (B4DT) for adolescents with obsessive-compulsive disorder (OCD). The aim of the current study was to replicate the initial results with a new sample of adolescents and different therapists at different sites across Norway. METHODS: Forty-three youths participated in treatment program. At pretreatment, posttreatment, and the three-month follow-up, OCD symptoms were assessed using the CY-BOCS interview, while the GAD-7 and PHQ-9 were administered to rate general anxiety symptoms and depressive symptoms. Acceptability and patient satisfaction with the treatment were rated with the CSQ-8. RESULTS: All symptoms were significantly reduced at posttreatment and follow-up. At posttreatment, 36 patients (85.71%) were defined as responders, while 29 patients (69.05%) achieved remission. At the three-month follow-up, 36 patients (92.3%) were defined as responders, while 33 patients (84.62%) were in remission. CSQ-8 scores indicated that the patients were highly satisfied with the treatment. CONCLUSIONS: The B4DT was successfully replicated in a new sample at different sites across Norway, which indicates that this treatment is generalizable, effective and acceptable to adolescents with OCD.

Patient adherence as a predictor of acute and long-term outcomes in concentrated exposure treatment for difficult-to-treat obsessive-compulsive disorder.

BACKGROUND: Exposure and response prevention (ERP) is considered the first-line psychotherapy for obsessive-compulsive disorder (OCD). Substantial research supports the effectiveness of ERP, yet a notable portion of patients do not fully respond while others experience relapse. Understanding poor outcomes such as these necessitates further research. This study investigated the role of patient adherence to ERP tasks in concentrated exposure treatment (cET) in a sample who had previously not responded to treatment or relapsed. METHOD: The present study included 163 adults with difficult-to-treat OCD. All patients received cET delivered during four consecutive days. Patients' treatment adherence was assessed using the Patient EX/RP Adherence Scale (PEAS-P) after the second and third day of treatment. OCD severity was evaluated at post-treatment, 3-month follow-up, and 1-year follow-up by independent evaluators. RESULTS: PEAS-P scores during concentrated treatment were associated with OCD-severity at post-treatment, 3-month follow-up, and 1-year follow-up. Moreover, PEAS-P scores predicted 12-month OCD severity adjusting for relevant covariates. Adherence also predicted work- and social functioning at 1-year follow-up. CONCLUSIONS: These results indicate that ERP adherence during the brief period of cET robustly relates to improvement in OCD symptoms and functioning in both the short and long term. Assessing adherence might identify patients at risk of poor outcomes, while improving adherence may enhance ERP for treatment resistant patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02656342.

The relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder: A systematic review and Meta-analysis.

BACKGROUND: This systematic review and meta-analysis explored the relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder (OCD). METHODS: We searched Pubmed, Scopus, Cochrane Library and PsychINFO databases until February 2023 for studies comparing patients with OCD and healthy controls on cognitive tests of compulsivity and impulsivity. The study followed PRISMA guidelines and was pre-registered on PROSPERO (CRD42021299017). RESULTS: Meta-analyses of 112 studies involving 8313 participants (4289 patients with OCD and 4024 healthy controls) identified significant impairments in compulsivity (g = -0.58, [95%CI -0.68, -0.47]; k = 76) and impulsivity (g = -0.48, [95%CI -0.57, -0.38]; k = 63); no significant difference between impairments. Medication use and comorbid psychiatric disorders were not significantly related to impairments. No associations were revealed with OCD severity, depression/anxiety, or illness duration. CONCLUSION: Cognitive phenotypes of compulsivity and impulsivity in patients with OCD appear to be orthogonal to clinical variables, including severity of OCD symptomatology. Their clinical impact is poorly understood and may require different clinical assessment tools and interventions.

Obsessive-Compulsive Disorder in Children and Adolescents.

Obsessive-compulsive disorder (OCD) in children and adolescents is a neurobehavioral condition that can lead to functional impairment in multiple domains and decreased quality of life. We review the clinical presentation, diagnostic considerations, and common comorbidities of pediatric OCD. An overview of the biological and psychological models of OCD is provided along with a discussion of developmental considerations in youth. We also describe evidence-based treatments for OCD in childhood and adolescence, including cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) and pharmacotherapy. Finally, research evaluating the delivery of CBT in different formats and modalities is discussed, and we conclude with suggestions for future research directions.

Targeting inflammatory signaling in obsessive compulsive disorder: a promising approach.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Approximately, around 2% to 3% percent of the general population experience symptoms of OCD over the course of their lifetime. OCD can lead to economic burden, poor quality of life, and disability. The characteristic features exhibited generally in OCD are continuous intrusive thoughts and periodic ritualized behaviours. Variations in genes, pathological function of Cortico-Striato-Thalamo-Cortical (CSTC) circuits and dysregulation in the synaptic conduction have been the major factors involved in the pathological progression of OCD. However, the basic mechanisms still largely unknown. Current therapies for OCD largely target monoaminergic neurotransmitters (NTs) in specific dopaminergic and serotonergic circuits. However, such therapies have limited efficacy and tolerability. Drug resistance has been one of the important reasons reported to critically influence the effectiveness of the available drugs. Inflammation has been a crucial factor which is believed to have a significant importance in OCD progression. A significant number of proinflammatory cytokines have been reportedly amplified in patients with OCD. Mechanisms of drug treatment involve attenuation of the symptoms via modulation of inflammatory signalling pathways, modification in brain structure, and synaptic plasticity. Hence, targeting inflammatory signaling may be considered as a suitable approach in the treatment of OCD. The present review focuses mainly on the significant findings from the animal and human studies conducted in this area, that targets inflammatory signaling in neurological conditions. In addition, it also focusses on the therapeutic approaches that target OCD via modification of the inflammatory signaling pathways.