Obsessive-compulsive disorder (OCD) is one of the most commonly seen mental disorders onset from childhood. The neural mechanisms underlying OCD development and maintenance remain poorly understood. Various empirical evidence from structural magnetic resonance imaging (MRI) studies has reported structural differences in grey matter (GM) among pediatric OCD patients. However, some of the findings diverge from others, and the association between GM and individual differences in pediatric OCD remains inconclusive. To address this gap, we conducted a meta-analysis to synthesize findings quantitatively.

The current research conducted a quantitative meta-analysis of voxel-based GM studies to elucidate existence of neural correlates in pediatric OCD. A whole brain-based d-mapping approach was utilized to explore GM changes and further analyze the relationship between GM and individual differences in pediatric OCD patients.

Thirteen studies were included with 288 patients and 273 controls. Compared with controls, pediatric OCD demonstrated significantly greater GM volume in the left insula (SDM value = 1.72, p < 0.005) and left superior frontal gyrus (SFG) (orbital part) (SDM value = 1.47, p < 0.005), whereas we showed lower GM volume in the right superior temporal gyrus (STG) (SDM value = -1.87, p < 0.005), left inferior parietal gyri (IPG) (SDM value = -1.60, p < 0.005), left middle occipital gyrus (MOG) (SDM value = -1.66, p < 0.005), and left inferior frontal gyrus (IFG) (SDM value = -1.69, p < 0.005). The increase in SFG (orbital part) and decrease IPG was commonly found in those without psychiatric comorbidities and treatment-naive subgroup. Meta-regression analysis revealed that longer OCD duration was associated with less GM volume in IPG (SDM value = -3.057, p < 0.005). Finally, the onset age and the OCD symptoms severity were positively associated with GM volume in the SFG (SDM z = 2.387, p < 0.005).

Our findings confirmed the most consistent GM differences in pediatric OCD, particularly in the MOG, IPG and SFG (orbital part), suggesting they are potential markers in pediatric OCD. Larger SFG (orbital part) and smaller IPG volumes are specific to those without comorbidities and untreated patients. The duration of OCD, symptom severity and onset age also influence GM structure. This research provides evidence of the underlying neuroanatomical characteristics of pediatric OCD.

PROSPERO CRD42024601906.

Currently, our understanding of the metabolic and immune pathways involved in obsessive-compulsive disorder (OCD), as well as the precise mechanisms by which metabolism and immunity impact brain activity and function, is limited. This study aimed to examine the alterations in serum metabolites, inflammatory markers, brain activity, and brain functional connectivity (FC) among individuals with OCD and investigate the relationship between these factors. The study included 55 individuals with moderate-to-severe OCD (either drug-naïve or not taking medication for at least eight weeks) and 54 healthy controls (HCs). The High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) technique was used to detect serum metabolites, whereas the enzyme-linked immunosorbent assay (ELISA) was utilized to identify inflammatory markers. The FC of the brain was investigated using resting-state functional magnetic resonance immaging(rs-fMRI). The findings demonstrated that individuals with OCD exhibited significant alterations in 11 metabolites compared to HCs. In particular, 10 of these metabolites exhibited an increase, while one metabolite displayed a decrease. Additionally, individuals with OCD experienced a marked elevation in the levels of five inflammatory factors (TNF-α, IL-1β, IL-2, IL-6, and IL-12). Rs-fMRI analysis revealed that individuals with OCD exhibited atypical FC in various brain regions, such as the postcentral gyrus, angular gyrus, and middle temporal gyrus. These specific brain areas are closely associated with sensory-motor processing, cognitive control, and emotion regulation. Further stepwise multiple regression analysis revealed that serum metabolite levels, particularly phosphatidylcholine, and inflammatory markers such as IL-1β could predict alterations in brain FC among individuals diagnosed with OCD. In summary, this study uncovered that individuals with OCD exhibit alterations in serum metabolites, inflammatory markers, brain activity, and FC. The findings suggest that these metabolites and inflammatory markers might play a role in the development and progression of OCD by affecting brain activity and the FC of neural networks.

Obsessive-compulsive disorder (OCD) is a highly heterogeneous disorder, with notable variations among cases in structural brain abnormalities. To address this heterogeneity, our study aimed to delineate OCD subtypes based on individualized gray matter morphological differences. We recruited 100 untreated, first-episode OCD patients and 106 healthy controls for structural imaging scans. Utilizing normative models of gray matter volume, we identified subtypes based on individual morphological abnormalities. Sensitivity analyses were conducted to validate the reproducibility of clustering outcomes. To gain deeper insights into the connectomic and molecular underpinnings of structural brain abnormalities in the identified subtypes, we investigated their associations with normal brain network architecture and the distribution of neurotransmitter receptors/transporters. Our findings revealed two distinct OCD subtypes exhibiting divergent patterns of structural brain abnormalities. Sensitivity analysis results confirmed the robustness of the identified subtypes. Subtype 1 displayed significantly increased gray matter volume in regions including the frontal gyrus, precuneus, insula, hippocampus, parahippocampal gyrus, amygdala, and temporal gyrus, while subtype 2 exhibited decreased gray matter volume in the frontal gyrus, precuneus, insula, superior parietal gyrus, temporal gyrus, and fusiform gyrus. When considering all patients collectively, structural brain abnormalities nullified. The identified subtypes were characterized by divergent disease epicenters. Specifically, subtype 1 showed disease epicenters in the middle frontal gyrus, while subtype 2 displayed disease epicenters in the striatum, thalamus and hippocampus. Furthermore, structural brain abnormalities in these subtypes displayed distinct associations with neurotransmitter receptors/transporters. The identified subtypes offer novel insights into nosology and the heterogeneous nature of OCD.

Transcranial magnetic stimulation (TMS) is a safe non-invasive treatment technique. We systematically reviewed randomised controlled trials (RCTs) applying TMS in obsessive compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) to analyse its therapeutic benefits and explore the relationship between cortical target and psychopathophysiology. We included 47 randomised controlled trials (35 for OCD) and found a 22.7 % symptom improvement for OCD and 29.4 % for PTSD. Eight cortical targets were investigated for OCD and four for PTSD, yielding similar results. Bilateral dlPFC-TMS exhibited the greatest symptom change (32.3 % for OCD, N = 4 studies; 35.7 % for PTSD, N = 1 studies), followed by right dlPFC-TMS (24.4 % for OCD, N = 8; 26.7 % for PTSD, N = 10), and left dlPFC-TMS (22.9 % for OCD, N = 6; 23.1 % for PTSD, N = 1). mPFC-TMS showed promising results, although evidence is limited (N = 2 studies each for OCD and PTSD) and findings for PTSD were conflicting. Despite clinical improvement, reviewed reports lacked a consistent and solid rationale for cortical target selection, revealing a gap in TMS research that complicates the interpretation of findings and hinders TMS development and optimisation. Future research should adopt a hypothesis-driven approach rather than relying solely on correlations from imaging studies, integrating neurobiological processes with affective, behavioural, and cognitive states, thereby doing justice to the complexity of human experience and mental illness.

Patients with obsessive-compulsive disorder are presumed to be at higher risk of sleep disorders due to the potential interference that persistent thoughts and compulsions may exert on sleep. Although there are studies on sleep findings in patients with obsessive-compulsive disorder, there are few systematic reviews on the presence of sleep disorders in patients with obsessive-compulsive disorder for adults and children. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed to perform a comprehensive search of PubMed and Web of Science using the MeSH terms "obsessive-compulsive disorder" and "sleep wake disorders". The exclusion criteria included publications not in English, studies performed on non-humans, abstracts, reviews, and meta-analyses. After applying the exclusion criteria, 17 studies qualified for inclusion in this systematic review. Nine studies were written about children and eight on adults. In the adult studies, sleep questionnaires, actigraphy and dim light melatonin onset showed delayed circadian rhythm in those with obsessive-compulsive disorder. Several studies showed an increased prevalence of insomnia in adult patients with obsessive-compulsive disorder. Overall, these studies showed sleep-onset and maintenance insomnia, and poor sleep quality. In the paediatric studies, sleep questionnaires revealed that paediatric patients with obsessive-compulsive disorder have increased sleep-related problems, including poor sleep quality, difficulty initiating and maintaining sleep, nightmares and sleepwalking. Two studies using actigraphy demonstrated a decreased total sleep time, increased wake after sleep onset and increased duration of awakening. Studies also showed an improvement in sleep symptoms with cognitive behavioural therapy. The systematic review has shown increased sleep-related problems and poor sleep quality both in adult and paediatric patients with obsessive-compulsive disorder. All patients with obsessive-compulsive disorder should therefore be screened for sleep-related problems to help in the overall outcome of treatment plans.

The high heterogeneity observed among patients with obsessive-compulsive disorder (OCD) underscores the need to identify neurophysiological OCD subtypes to facilitate personalized diagnosis and treatment. In this study, our aim was to identify potential OCD subtypes based on individualized functional connectome abnormalities. We recruited a total of 99 patients with OCD and 104 healthy controls (HCs) matched for demographic characteristics. Individualized functional connectome abnormalities were obtained using normative models of functional connectivity strength (FCS) and used as features to unveil OCD subtypes. Sensitivity analyses were conducted to assess the reproducibility and robustness of the clustering outcomes. Patients exhibited significant intersubject heterogeneity in individualized functional connectome abnormalities. Two subtypes with distinct patterns of FCS abnormalities relative to HCs were identified. Subtype 1 patients primarily exhibited significantly decreased FCS in regions including the frontal gyrus, insula, hippocampus, and precentral/postcentral gyrus, whereas subtype 2 patients demonstrated increased FCS in widespread brain regions. When all patients were combined, no significant differences were observed. Additionally, the identified subtypes showed significant differences in age of onset. Furthermore, sensitivity analyses confirmed the reproducibility of our subtyping results. In conclusion, the identified OCD subtypes shed new light on the taxonomy and neurophysiological heterogeneity of OCD.

Obsessional slowness (OS) is characterized by a syndrome of extreme slowness in doing ordinary, day-to-day activities. Several scholars regarded OS as secondary to obsessive compulsive disorder (OCD). Therefore, it is commonly thought to be the consequence of extensive rituals and has been paid minimal attention in its own right. A combination of behavior therapy and aromatherapy are recommended for treatment of this condition. However, the outcome is often frustrating. Reports of surgical management for OS are limited.

She had symptoms characterized by repeated checking and progressive slowness in self-care behavior.

At the age of 19, the patient had the first presentation. The patient was diagnosed with a case of OCD with obsessional slowness according to the International Classification of Diseases and Related Health Problems (ICD-10).

Considering the lack of a response to pharmacotherapy and cognitive behavioral therapy (CBT), we treated this case with anterior capsulotomy and accumbensotomy.

Moderate somnolence, urticaria, juvenile behavior, mild short-term memory impairment and slight nonsense were noted during the first postoperative days. At 10 months, the patient's OCD symptoms recovered nearly to her preoperative level. The OS symptom also had an obvious rebound at 10 months. Through comprehensive judgment, we decided to choose accumbensotomy. At 9 months after the accumbensotomy, the OCD symptoms started to rebound. Soon after, the OS symptoms also recurred. At the last timepoint of 30 months, the patient's OCD and OS symptoms had completely rebounded. This time, the patient and parents refused any treatment.

This case suggests that OCD with OS, as a special category, might not be suitable for stereotactic neurosurgery. Furthermore, multiple surgeries in this kind of OCD patient should be considered with as much caution as much as possible.

Astrocytes are morphologically complex cells that serve essential roles. They are widely implicated in central nervous system (CNS) disorders, with changes in astrocyte morphology and gene expression accompanying disease. In the Sapap3 knockout (KO) mouse model of compulsive and anxiety-related behaviors related to obsessive-compulsive disorder (OCD), striatal astrocytes display reduced morphology and altered actin cytoskeleton and Gi-G-protein-coupled receptor (Gi-GPCR) signaling proteins. Here, we show that normalizing striatal astrocyte morphology, actin cytoskeleton, and essential homeostatic support functions by targeting the astrocyte Gi-GPCR pathway using chemogenetics corrected phenotypes in Sapap3 KO mice, including anxiety-related and compulsive behaviors. Our data portend an astrocytic pharmacological strategy for rescuing phenotypes in brain disorders that include compromised astrocyte morphology and tissue support.

Individuals suffering from obsessive compulsive disorder (OCD) and schizophrenia (SCZ) frequently exhibit symptoms of cognitive disassociations, which are linked to poor functional integration among brain regions. The loss of functional integration can be assessed using graph metrics computed from functional connectivity matrices (FCMs) derived from neuroimaging data. A healthy brain at rest is known to exhibit small-world features with high clustering coefficients and shorter path lengths in contrast to random networks. The aim of this study was to compare the small-world properties of prefrontal cortical functional networks of healthy subjects with OCD and SCZ patient groups by use of hemodynamic data obtained with functional near infrared spectroscopy (fNIRS). 13 healthy subjects and 47 patients who were clinically diagnosed with either OCD (N = 21) or SCZ (N = 26) completed a Stroop test while their prefrontal cortex (PFC) hemodynamics were monitored with fNIRS. The Stroop test had a block design consisting of neutral, congruent and incongruent stimuli. For each subject and stimuli type, FCMs were derived separately which were then used to compute small world features that included (i) global efficiency (GE), (ii) clustering coefficient (CC), (iii) modularity (Q), and (iv) small-world parameter ( σ ). Small-world features of patients exhibited random networks which were indicated by higher GE and lower CC values when compared to healthy controls, implying a higher neuronal operational cost.

Dopamine modulates working memory in the prefrontal cortex (PFC) and is crucial for obsessive-compulsive disorder (OCD). However, the mechanism is unclear. Here we establish a biophysical model of the effect of dopamine (DA) in PFC to explain the mechanism of how high dopamine concentrations induce persistent neuronal activities with the network plunging into a deep, stable attractor state. The state develops a defect in working memory and tends to obsession and compulsion. Weakening the reuptake of dopamine acts on synaptic plasticity according to Hebbian learning rules and reward learning, which in turn affects the strength of neuronal synaptic connections, resulting in the tendency of compulsion and learned obsession. In addition, we elucidate the potential mechanisms of dopamine antagonists in OCD, indicating that dopaminergic drugs might be available for treatment, even if the abnormality is a consequence of glutamate hypermetabolism rather than dopamine. The theory highlights the significance of early intervention and behavioural therapies for obsessive-compulsive disorder. It potentially offers new approaches to dopaminergic pharmacotherapy and psychotherapy for OCD patients.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating illness that has been considered a polygenic and multifactorial disorder, challenging effective therapeutic interventions. Although invaluable advances have been obtained from human and rodent studies, several molecular and mechanistic aspects of OCD etiology are still obscure. Thus, the use of non-traditional animal models may foster innovative approaches in this field, aiming to elucidate the underlying mechanisms of disease from an evolutionary perspective. The zebrafish (Danio rerio) has been increasingly considered a powerful organism in translational neuroscience research, especially due to the intrinsic features of the species. Here, we outline target mechanisms of OCD for translational research, and discuss how zebrafish-based models can contribute to explore neurobehavioral aspects resembling those found in OCD. We also identify possible advantages and limitations of potential zebrafish-based models, as well as highlight future directions in both etiological and therapeutic research. Lastly, we reinforce the use of zebrafish as a promising tool to unravel the biological basis of OCD, as well as novel pharmacological therapies in the field.

Transcranial direct current stimulation (tDCS) has been used with increasing frequency as a therapeutic tool to alleviate clinical symptoms of obsessive compulsive-disorder (OCD). However, little is known about the effects of tDCS on neurocognitive functioning among OCD patients. The aim of this review was to provide a comprehensive overview of the literature examining the effects of tDCS on specific neurocognitive functions in OCD. A literature search following PRISMA guidelines was conducted on the following databases: PubMed, PsycINFO, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. The search yielded 4 results: one randomized, sham-controlled study (20 patients), one randomized, controlled, partial crossover trial (12 patients), one open-label study (5 patients), and one randomized, double-blind, sham-controlled, parallel-group trial (37 patients). A total of 51 patients received active tDCS with some diversity in electrode montages targeting the dorsolateral prefrontal cortex, the pre-supplementary motor area, or the orbitofrontal cortex. tDCS was associated with improved decision-making in study 1, enhanced attentional monitoring and response inhibition in study 2, improved executive and inhibitory control in study 3, and reduced attentional bias and improved response inhibition and working memory in study 4. Limitations of this review include its small sample, the absence of a sham group in half of the studies, and the heterogeneity in tDCS parameters. These preliminary results highlight the need for future testing in randomized, sham-controlled trials to examine whether and how tDCS induces relevant cognitive benefits in OCD.

This review summarizes the current state of neuroimaging research on obsessive-compulsive disorder (OCD) using diffusion tensor imaging (DTI), which allows for the examination of white matter abnormalities in the brain. DTI studies on individuals with obsessive-compulsive disorder (OCD) consistently demonstrate widespread reductions in white matter integrity in various regions of the brain, including the corpus callosum, anterior and posterior cingulate cortex, and prefrontal cortex, which are involved in emotion regulation, decision-making, and cognitive control. However, the reviewed studies often have small sample sizes, and findings vary between studies, highlighting the need for larger and more standardized studies. Furthermore, discerning between causal and consequential effects of OCD on white matter integrity poses a challenge. Addressing this issue may be facilitated through longitudinal studies, including those evaluating the impact of treatment interventions, to enhance the accuracy of DTI data acquisition and processing, thereby improving the validity and comparability of study outcomes. In summary, DTI studies provide valuable insights into the neural circuits and connectivity disruptions in OCD, and future studies may benefit from standardized data analysis and larger sample sizes to determine whether structural abnormalities could be potential biomarkers for early identification and treatment of OCD.

Schedule-induced drinking (SID) reproduces an excessive and repetitive behavioural pattern that has led to propose this procedure as an animal model to study compulsive behaviours. Although it is known that cannabis can cause several adverse effects, in recent years there has been great interest in the medical application of cannabis derivatives for obsessive-compulsive related disorders.

The present study investigated the effects of repeated THC administration on rates of previously acquired SID, as well as the possible alteration of its temporal distribution along inter-food intervals.

Male Wistar rats acquired SID under a 30 min fixed-time 30-sec food delivery schedule (from 30 to 43 sessions to reach a stable level). Thereafter, 5 or 10 mg/kg daily i.p. injections of THC or vehicle were repeatedly administered for 7 days to evaluate the effects on SID.

Repeated THC administration at a dose of 5 mg/kg resulted in an increase on licking. Surprisingly, no effects on SID were observed with the 10 mg/kg dose. However, magazine entries were reduced with both THC doses. THC also modified the temporal distributions of licking and magazine entries during inter-food intervals.

The present results show that repeated THC administration may (i) increase induced licking at moderate doses, (ii) reduce magazine entries, and (iii) affect the temporal pattern of SID. These findings suggest that THC does not appear to be beneficial to reduce compulsive behaviour in this animal model, while another collateral effect of THC -such as a greater habitual-like behaviour- needs to be considered.

Compulsive behaviors are a hallmark symptom of obsessive compulsive disorder (OCD). Striatal hyperactivity has been linked to compulsive behavior generation in correlative studies in humans and causal studies in rodents. However, the contribution of the two distinct striatal output populations to the generation and treatment of compulsive behavior is unknown. These populations of direct and indirect pathway-projecting spiny projection neurons (SPNs) have classically been thought to promote or suppress actions, respectively, leading to a long-held hypothesis that increased output of direct relative to indirect pathway promotes compulsive behavior. Contrary to this hypothesis, here we find that indirect pathway hyperactivity is associated with compulsive grooming in the Sapap3-knockout mouse model of OCD-relevant behavior. Furthermore, we show that suppression of indirect pathway activity using optogenetics or treatment with the first-line OCD pharmacotherapy fluoxetine is associated with reduced grooming in Sapap3-knockouts. Together, these findings highlight the striatal indirect pathway as a potential treatment target for compulsive behavior.

Tics are sudden, repetitive movements or vocalizations. Tic disorders, such as Tourette syndrome (TS), are contributed by the interplay of genetic risk factors and environmental variables, leading to abnormalities in the functioning of the cortico-striatal-thalamo-cortical (CSTC) circuitry. Various neurotransmitter systems, such as gamma-aminobutyric acid (GABA) and dopamine, are implicated in the pathophysiology of these disorders. Building on the evidence that tic disorders are predominant in males and exacerbated by stress, emerging research is focusing on the involvement of neuroactive steroids, including dehydroepiandrosterone sulfate (DHEAS) and allopregnanolone, in the ontogeny of tics and other phenotypes associated with TS. Emerging evidence indicates that DHEAS levels are significantly elevated in the plasma of TS-affected boys, and the clinical onset of this disorder coincides with the period of adrenarche, the developmental stage characterized by a surge in DHEAS synthesis. On the other hand, allopregnanolone has garnered particular attention for its potential to mediate the adverse effects of acute stress on the exacerbation of tic severity and frequency. Notably, both neurosteroids act as key modulators of GABA-A receptors, suggesting a pivotal role of these targets in the pathophysiology of various clinical manifestations of tic disorders. This review explores the potential mechanisms by which these and other neuroactive steroids may influence tic disorders and discusses the emerging therapeutic strategies that target neuroactive steroids for the management of tic disorders.

Obsessive-compulsive symptoms (OCS) are relatively common during adolescence although most individuals do not meet diagnostic criteria for obsessive-compulsive disorder (OCD). Nonetheless, OCS during adolescence are associated with comorbid psychopathologies and behavioral problems. Heightened levels of environmental stress and greater functional connectivity between the somatomotor network and putamen have been previously associated with elevated OCS in OCD patients relative to healthy controls. However, the interaction of these factors within the same sample of individuals has been understudied. This study examined somatomotor-putamen resting state connectivity, stress, and their interaction on OCS in adolescents from 9-12 years of age. Participants (n = 6386) were drawn from the ABCD Study 4.0 release. Multilevel modeling was used to account for nesting in the data and to assess changes in OCS in this age range. Stress moderated the association between somatomotor-putamen connectivity and OCS (β = 0.35, S.E. = 0.13, p = 0.006). Participants who reported more stress than their average and had greater somatomotor-left putamen connectivity reported more OCS, whereas participants who reported less stress than their average and had greater somatomotor-left putamen connectivity reported less OCS. These data suggest that stress differentially affects the direction of association between somatomotor-putamen connectivity and OCS. Individual differences in the experience or perception of stress may contribute to more OCS in adolescents with greater somatomotor-putamen connectivity.

Glutamate is an important neurotransmitter known to be effective in obsessive-compulsive disorder (OCD). The aim of this study is to investigate the relationship between the DLGAP1 gene encoding the scaffold protein of ionotropic glutamate receptors and the SLC1A1 gene encoding the glutamate transporter protein with OCD. Study groups consisted of 95 patients with OCD and 100 healthy controls. The severity of OCD in the patient group was determined by using the Y-BOCS. Single nucleotide polymorphisms of rs11081062 (C/T) in DLGAP1 and rs587777696 (C/T) in SLC1A1 were analyzed by real-time PCR. Levels of SLC1A1 protein were determined by ELISA. A significant difference was found between genotype distributions of rs11081062 in DLGAP1 in study groups (p < 0.001). No significant association was found rs587777696 in SLC1A1 in OCD patients and controls. SLC1A1 protein levels were found to be lower in OCD patients compared to controls (p = 0.005). According to OCD risk estimates for genotypes distributions of rs11081062 in DLGAP1, having CT + TT genotypes was associated with the occurrence of sexual and religious obsessions and counting compulsions (p = 0.038, OR = 2.98; p = 0.033, OR = 3.43; p = 0.035, OR = 2.66, respectively). CT genotype in DLGAP1 rs11081062 polymorphism was found to increase the risk of OCD in the female gender (p = 0.042, OR = 3.01). This study suggests that rs11081062 in DLGAP1 may be associated with OCD and that SLC1A1 protein levels may be involved in the occurrence of OCD. We believe that our research can contribute to the understanding of the importance of glutamate in OCD.

Animals often behave repetitively and predictably. These repetitive behaviors can have a component that is learned and ingrained as habits, which can be evolutionarily advantageous as they reduce cognitive load and the expenditure of attentional resources. Repetitive behaviors can also be conscious and deliberate, and may occur in the absence of habit formation, typically when they are a feature of normal development in children, or neuropsychiatric disorders. They can be considered pathological when they interfere with social relationships and daily activities. For instance, people affected by obsessive-compulsive disorder, autism spectrum disorder, Huntington's disease and Gilles de la Tourette syndrome can display a wide range of symptoms like compulsive, stereotyped and ritualistic behaviors. The striatum nucleus of the basal ganglia is proposed to act as a master regulator of these repetitive behaviors through its circuit connections with sensorimotor, associative, and limbic areas of the cortex. However, the precise mechanisms within the striatum, detailing its compartmental organization, cellular specificity, and the intricacies of its downstream connections, remain an area of active research. In this review, we summarize evidence across multiple scales, including circuit-level, cellular, and molecular dimensions, to elucidate the striatal mechanisms underpinning repetitive behaviors and offer perspectives on the implicated disorders. We consider the close relationship between behavioral output and transcriptional changes, and thereby structural and circuit alterations, including those occurring through epigenetic processes.

Cognitive behaviour therapy with exposure and response prevention is efficient in treating patients with obsessive-compulsive disorder (OCD). Nevertheless, it would be helpful for many patients to complement the therapeutic treatment with acceptance strategies to further increase the therapeutic benefit. The aim of the present study was to examine neurobiological responses to acceptance and intensification strategies during symptom provocation alongside the psychotherapeutic process.

A total of 23 patients diagnosed with OCD (subtype: washing/contamination fear) was instructed to utilise either an acceptance strategy (ACS) or an intensification strategy (INS) to cope with their emotional and cognitive reactions to personalised symptom-triggering and neutral pictures. Fourteen patients participated twice: at the beginning [T1] and at the end [T2] of an inpatient multimodal treatment including cognitive behaviour therapy with response prevention to assess functional variations.

For the contrast of T1 and T2, ACS showed increased brain activity in the left inferior frontal gyrus (IFG), left caudate body, and posterior cingulate gyrus (PCC). They also showed decreased activity in the left anterior insula. INS showed decreased activation in right lingual gyrus and right caudate body. At T2, ACS showed increased activation compared to INS in the left cerebrum: IFG, caudate nucleus, middle and superior temporal gyrus, and PCC/cuneus. For the comparison of T1 and T2, the ACS revealed increased brain activity in the left IFG, left caudate body, and right inferior parietal lobe. It showed decreased activity in the left anterior insula. The INS revealed decreased activity in right lingual gyrus and right caudate body.The psychometric questionnaires suggested that patients were able to reduce obsession, compulsion, and depression symptoms. Furthermore, patients rated the ACS as more useful for themselves compared with the INS.

The increased left IFG activity using ACS (T1 vs. T2) could be interpreted as a better inhibitory top-down process, while the increased PCC response might be due to a better reappraisal strategy after therapy. ACS seems to mobilise neuronal activations under therapy, especially in the left hemisphere. Both strategies showed reductions in emotional networks as a neuronal correlate of therapy success. Overall, ACS may be more efficient than INS, as rated by the patients and as in accordance with neurobiological findings.

Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiopathogenesis, according to various neuroimaging studies, seems to be linked to selective dysfunctions in regions within the cortico-striatal-thalamo-cortical circuit. Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line therapy for OCD but their neurobiological effects on the brain is only partially understood. Therefore, the aim of this review is to highlight structural and functional brain imaging modifications induced by SSRIs treatment.

A literature search on PubMed, Psych-Info and Embase database was performed. Studies including patients with OCD that analyzed the effect of SSRIs through structural and functional Magnetic Resonance Imaging were selected. Seven relevant studies were considered eligible for the present review.

Overall, the results of the reviewed studies showed that SSRIs treatment seems to normalize structural, in terms of the white matter and gray matter volumes, and functional activity alterations observed in OCD patients, especially in regions within the prefrontal cortex and striatum.

The poor design of the studies, the small and heterogeneous samples, differences in age, gender, illness course, comorbidities, treatment protocols and the different magnetic fields used make it difficult to generalize the results.

From the available evidence it emerged that SSRIs treatment has proven to be effective in normalizing brain structural and functional alterations observed in OCD patients. However, future neuroimaging investigations should focus on long-term effects of drugs on brain structure and function in OCD patients through longitudinal approaches in order to identify more effective treatments for these patients.

Disruptions in large-scale brain connectivity are hypothesized to contribute to psychiatric disorders, including schizophrenia, bipolar I disorder, and attention-deficit/hyperactivity disorder. However, high inter-individual variation among patients with psychiatric disorders hinders achievement of unified findings. To this end, we adopted a newly proposed method to resolve heterogeneity of differential structural covariance network in schizophrenia, bipolar I disorder, and attention-deficit/hyperactivity disorder. This method could infer individualized structural covariance aberrance by assessing the deviation from healthy controls. T1-weighted anatomical images of 114 patients with psychiatric disorders (schizophrenia: n = 37; bipolar I disorder: n = 37; attention-deficit/hyperactivity disorder: n = 37) and 110 healthy controls were analyzed to obtain individualized differential structural covariance network. Patients exhibited tremendous heterogeneity in profiles of individualized differential structural covariance network. Despite notable heterogeneity, patients with the same disorder shared altered edges at network level. Moreover, individualized differential structural covariance network uncovered two distinct psychiatric subtypes with opposite differences in structural covariance edges, that were otherwise obscured when patients were merged, compared with healthy controls. These results provide new insights into heterogeneity and have implications for the nosology in psychiatric disorders.

The Seeking Proxies for Internal States (SPIS) model of obsessive-compulsive disorder (OCD) explains symptoms of OCD as stemming from attenuated access to internal states, which is compensated for by using proxies, which are indices of these states that are more discernible or less ambiguous. Internal states in the SPIS model are subjective states that are not accessible to others, encompassing physiological states, motivations, preferences, memories, and emotions. Compensatory proxies in OCD include fixed rules and rituals as well as seeking and relying on external information. In the present review, we outline the SPIS model and describe its basic tenets. We then use the SPIS conceptualization to explain two pivotal OCD-related phenomena - obsessive doubt and compulsive rituals. Next, we provide a detailed overview of current empirical evidence supporting the SPIS in several domains, including physiological states, emotions, sense of understanding, decision-making, and sense of agency. We conclude by discussing possible neural correlates of the difficulty in accessing internal states, focusing on the anterior insular cortex (AIC) and highlighting potential clinical implications of the model to the treatment of OCD.

The intricate neural pathways involved in obsessive-compulsive disorder (OCD) affect areas of our brain that control executive functioning, organization, and planning. OCD is a chronic condition that can be debilitating, afflicting millions of people worldwide. The lifetime prevalence of OCD in the US is 2.3%. OCD is predominantly characterized by obsessions consisting of intrusive and unwanted thoughts, often with impulses that are strongly associated with anxiety. Compulsions with OCD encompass repetitive behaviors or mental acts to satisfy their afflicted obsessions or impulses. While these factors can be unique to each individual, it has been widely established that the etiology of OCD is complex as it relates to neuronal pathways, psychopharmacology, and brain chemistry involved and warrants further exploration.

Obsessive-compulsive disorder (OCD) is a chronic disabling disease with often unsatisfactory therapeutic outcomes. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has broadened the diagnostic criteria for OCD, acknowledging that some OCD patients may lack insight into their symptoms. Previous studies have demonstrated that insight can impact therapeutic efficacy and prognosis, underscoring its importance in the treatment of mental disorders, including OCD. In recent years, there has been a growing interest in understanding the influence of insight on mental disorders, leading to advancements in related research. However, to the best of our knowledge, there is dearth of comprehensive reviews on the topic of insight in OCD. In this review article, we aim to fill this gap by providing a concise overview of the concept of insight and its multifaceted role in clinical characteristics, neuroimaging mechanisms, and treatment for OCD.

The pathogenesis of obsessive-compulsive disorder (OCD) may involve altered dendritic morphology, but in vivo imaging of neurite morphology in OCD remains limited. Such changes must be interpreted functionally within the context of the multimodal neuroimaging approach to OCD.

To examine whether dendritic morphology is altered in patients with OCD compared with healthy controls (HCs) and whether such alterations are associated with other brain structural metrics in pathological networks.

This case-control study used cross-sectional data, including multimodal brain images and clinical symptom assessments, from 108 patients with OCD and 108 HCs from 2014 to 2017. Patients with OCD were recruited from Shanghai Mental Health Center, Shanghai, China, and HCs were recruited via advertisements. The OCD group comprised unmedicated adults with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) diagnosis of OCD, while the HCs were adults without any DSM-IV diagnosis, matched for age, sex, and education level. Data were analyzed from September 2019 to April 2023.

DSM-IV diagnosis of OCD.

Multimodal brain imaging was used to compare neurite microstructure and classic morphometries between patients with OCD and HCs. The whole brain was searched to identify regions exhibiting altered morphology in patients with OCD and explore the interplay between the brain metrics representing these alterations. Brain-symptom correlations were analyzed, and the performance of different brain metric configurations were evaluated in distinguishing patients with OCD from HCs.

Among 108 HCs (median [IQR] age, 26 [23-31] years; 50 [46%] female) and 108 patients with OCD (median [IQR] age, 26 [24-31] years; 46 [43%] female), patients with OCD exhibited deficient neurite density in the right lateral occipitoparietal regions (peak t = 3.821; P ≤ .04). Classic morphometries also revealed widely-distributed alterations in the brain (peak t = 4.852; maximum P = .04), including the prefrontal, medial parietal, cingulate, and fusiform cortices. These brain metrics were interconnected into a pathological brain network associated with OCD symptoms (global strength: HCs, 0.253; patients with OCD, 0.941; P = .046; structural difference, 0.572; P < .001). Additionally, the neurite density index exhibited high discriminatory power in distinguishing patients with OCD from HCs (accuracy, ≤76.85%), and the entire pathological brain network also exhibited excellent discriminative classification properties (accuracy, ≤82.87%).

The findings of this case-control study underscore the utility of in vivo imaging of gray matter dendritic density in future OCD research and the development of neuroimaging-based biomarkers. They also endorse the concept of connectopathy, providing a potential framework for interpreting the associations among various OCD symptom-related morphological anomalies.

Background: Obsessive-compulsive disorder (OCD) and panic disorder (PD) are debilitating psychiatric conditions, yet their underlying neurobiological differences remain underexplored. This study aimed to directly compare resting-state EEGs in patients with OCD and PD, without a healthy control group, using the eLORETA method. Methods: We collected retrospective EEG data from 24 OCD patients and 22 PD patients who were hospitalized due to significant impairment in daily life functions. eLORETA was used to analyze the EEG data. Results: Heightened theta activity was observed in the anterior cingulate cortex (ACC) of OCD patients compared to PD patients (PD vs. OCD, t = -2.168, p < 0.05). Conversely, higher gamma activity was found in the medial frontal gyrus (MFG) and paracentral lobule (PCL) in PD patients (PD vs. OCD, t = 2.173, p < 0.05). Conclusions: Our findings highlight neurobiological differences between OCD and PD patients. Specifically, the increased theta activity in the ACC for OCD patients and elevated gamma activity in the MFG and PCL for PD patients offer preliminary insights into the neural mechanisms of these disorders. Further studies are essential to validate these results and delve deeper into the neural underpinnings.

Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders.

Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed.

Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network.

These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.

In this study, we utilized proton magnetic resonance spectroscopy (MRS) to understand the role of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) of OCD patients in the pregenual anterior cingulate cortex (pgACC). In total, 54 patients with OCD and 54 healthy controls (HC) matched for age and sex were included in the study. They underwent MRS in the pgACC region to calculate the concentrations of Glu, Gln, GABA, and Glu + Gln (Glx). After quality control of the MRS data, 21 OCD and 21 HC were statistically analyzed. The severity of symptoms were evaluated using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the statistical analysis, we compared differences between groups for the metabolites; in the OCD we analyzed the correlations with symptom severity, medication status, age, and duration of illness. A significant decrease in Glx, in Glu, and in Gln in the pgACC were observed in the OCD compared to HC. The correlation statistics showed a significant positive correlation between Glu levels and the YBOCS compulsions subscale. The results indicate that patients with OCD present a disturbance in glutamatergic metabolism in the pgACC. The results also demonstrate that these changes correlate with the severity of compulsions.

Although in 2017 a repetitive transcranial magnetic stimulation (rTMS) protocol received Food and Drug Administration approval for the first time for the treatment of obsessive-compulsive disorder (OCD), which neural target and which protocol should be used for OCD are still debated. The aim of the present study was to perform a systematic review and meta-analysis of the available open and sham-controlled trials.

The primary analysis included a pairwise meta-analysis (over 31 trials), and then subgroup analyses were performed for each targeted brain area. Meta-regression analyses explored the possible moderators of effect size.

The pairwise meta-analysis showed a significant reduction in OCD symptoms following active rTMS (g = -0.45 [95%CI: -0.62, -0.29]) with moderate heterogeneity (I² = 34.9%). Subgroup analyses showed a significant effect of rTMS over the bilateral pre-SMA (supplementary motor area), the DLPFC (dorsolateral prefrontal cortex), the ACC/mPFC (anterior cingulate cortex and medial prefrontal cortex), and the OFC (orbitofrontal cortex). No moderators of the effect size emerged.

TMS of several brain targets represents a safe and effective treatment option for OCD patients. Further studies are needed to help clinicians to individualize TMS protocols and targets for each patient.

There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (¹H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.

Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing distress. Symptoms can cause severe distress and functional impairment. OCD affects 2% to 3% of the population and is ranked within the 10 leading neuropsychiatric causes of disability. Cortico-striatal-thalamo-cortical circuitry dysfunction has been implicated in OCD, including altered brain activation and connectivity. Complex glutamatergic signaling dysregulation within cortico-striatal circuitry has been proposed in OCD. Data obtained by several studies indicate reduced glutamatergic concentrations in the anterior cingulate cortex, combined with overactive glutamatergic signaling in the striatum and orbitofrontal cortex. A growing number of randomized controlled trials have assessed the utility of different glutamate-modulating drugs as augmentation medications or monotherapies for OCD, including refractory OCD. However, there are relevant variations among studies in terms of patients' treatment resistance, comorbidity, age, and gender. At present, 4 randomized controlled trials are available on the efficacy of memantine as an augmentation medication for refractory OCD.

Our study's main purpose is to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of moderate to severe OCD. The study's second aim is to evaluate the effect of memantine on cognitive functions in patients with OCD. The third aim is to investigate if responses to memantine are modulated by variables such as gender, symptom subtypes, and the duration of untreated illness.

Investigators intend to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of patients affected by severe refractory OCD. Participants will be rated via the Yale-Brown Obsessive Compulsive Scale at baseline and at 2, 4, 6, 8, 10, and 12 months. During the screening period and T4 and T6 follow-up visits, all participants will undergo an extensive neuropsychological evaluation. The 52-week study duration will consist of 4 distinct periods, including memantine titration and follow-up periods.

Recruitment has not yet started. The study will be conducted from June 2023 to December 2024. Results are expected to be available in January 2025. Throughout the slow-titration period, we will observe the minimum effective dose of memantine, and the follow-up procedure will detail its residual efficacy after drug withdrawal.

The innovation of this research proposal is not limited to the evaluation of the efficacy and safety of memantine as an augmentation medication for OCD. We will also test if memantine acts as a pure antiobsessive medication or if memantine's ability to improve concentration and attention mimics an antiobsessive effect.

ClinicalTrials.gov NCT05015595; https://clinicaltrials.gov/ct2/show/NCT05015595.

PRR1-10.2196/39223.

Obsessive-compulsive disorder (OCD) is characterized by recurring obsessive thoughts and repetitive behaviors that are often associated with anxiety and perturbations in cortico-striatal signaling. Given the suboptimal response of OCD to current serotonergic interventions, there is a need to better understand the psychobiological mechanisms that may underlie the disorder. In this regard, investigations into adenosinergic processes might be fruitful. Indeed, adenosine modulates both anxiety- and motor behavioral output. Thus, we aimed to explore the potential associations between compulsive-like large nest building (LNB) behavior in deer mice, anxiety and adenosinergic processes. From an initial pool of 120 adult deer mice, 34 normal nest building (NNB)- and 32 LNB-expressing mice of both sexes were selected and exposed to either a normal water (wCTRL) or vehicle control (vCTRL), lorazepam (LOR) or istradefylline (ISTRA) for 7- (LOR) or 28 days after which nesting assessment was repeated and animals screened for anxiety-like behavior in an anxiogenic open field. Mice were then euthanized, the striatal tissue removed on ice and the adenosine A_2A receptor expression quantified. Our findings indicate that NNB and LNB behavior are not distinctly associated with measures of generalized anxiety and that ISTRA-induced changes in nesting expression are dissociated from changes in anxiety scores. Further, data from this investigation show that nesting in deer mice is directly related to striatal adenosine signaling, and that LNB is founded upon a lower degree of adenosinergic A_2A stimulation.

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.

Obsessive-compulsive disorder (OCD) patients need novel therapeutic interventions since most experience residual symptoms despite treatment. Converging evidence suggest that OCD involves dysfunction of limbic cortico-striato-thalamo-cortical loops, including the medial prefrontal cortex (mPFC) and dorsal anterior cingulate cortex (dACC), that tends to normalize with successful treatment. Recently, three repetitive transcranial magnetic stimulation (rTMS) coils were FDA-cleared for treatment-refractory OCD. This review presents on-label and off-label clinical evidence and relevant physical characteristics of the three coils. The Deep TMS™ H7 Coil studies' point to efficacy of mPFC-dACC stimulation, while no clear target stems from the small heterogenous D-B80 and figure-8 coils studies.

Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are accompanied by deficits in behavioural flexibility. In reinforcement learning, this inflexibility can reflect asymmetric learning from outcomes above and below expectations. In alternative frameworks, it reflects perseveration independent of learning. Here, we examine evidence for asymmetric reward-learning in OCD and PG by leveraging model-based functional magnetic resonance imaging (fMRI). Compared with healthy controls (HC), OCD patients exhibited a lower learning rate for worse-than-expected outcomes, which was associated with the attenuated encoding of negative reward prediction errors in the dorsomedial prefrontal cortex and the dorsal striatum. PG patients showed higher and lower learning rates for better- and worse-than-expected outcomes, respectively, accompanied by higher encoding of positive reward prediction errors in the anterior insula than HC. Perseveration did not differ considerably between the patient groups and HC. These findings elucidate the neural computations of reward-learning that are altered in OCD and PG, providing a potential account of behavioural inflexibility in those mental disorders.

Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal-striatal-thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative to controls. However, as adult OCD patients often have high rates of co-morbid anxiety and long durations of illness, little is known about the functional connectivity of these networks in relation to OCD specifically, or in young patients near illness onset.

In this study, unmedicated female patients with OCD (ages 8-21 years, n = 23) were compared to age-matched female patients with anxiety disorders (n = 26), and healthy female youth (n = 44). Resting-state functional connectivity was used to determine the strength of functional connectivity within and between OST, CON, and DMN.

Functional connectivity within the CON was significantly greater in the OCD group as compared to the anxiety and healthy control groups. Additionally, the OCD group displayed greater functional connectivity between OST and CON compared to the other two groups, which did not differ significantly from each other.

Our findings indicate that previously noted network connectivity differences in pediatric patients with OCD were likely not attributable to co-morbid anxiety disorders. Moreover, these results suggest that specific patterns of hyperconnectivity within CON and between CON and OST circuitry may characterize OCD relative to non-OCD anxiety disorders in youth. This study improves understanding of network dysfunction underlying pediatric OCD as compared to pediatric anxiety.

Schizophrenia (SCZ) is a severe mental illness mainly characterized by a number of psychiatric symptoms. Obsessive-compulsive disorder (OCD) is a long-lasting and devastating mental disorder. SCZ has high co-occurrence with OCD resulting in the emergence of a concept entitled "schizo-obsessive disorder" as a new specific clinical entity with more severe psychiatric symptoms. Many studies have been done on SCZ and OCD, but the common pathogenesis between them is not clear yet. Therefore, this study aimed to identify shared genetic basis, potential biomarkers and therapeutic targets between these two disorders. Gene sets were extracted from the Geneweaver and Harmonizome databases for each disorder. Interestingly, the combination of both sets revealed 89 common genes between SCZ and OCD, the most important of which were BDNF, SLC6A4, GAD1, HTR2A, GRIN2B, DRD2, SLC6A3, COMT, TH and DLG4. Then, we conducted a comprehensive bioinformatics analysis of the common genes. Receptor activity as the molecular functions, neuron projection and synapse as the cellular components as well as serotonergic synapse, dopaminergic synapse and alcoholism as the pathways were the most significant commonalities in enrichment analyses. In addition, transcription factor (TFs) analysis predicted significant TFs such as HMGA1, MAPK14, HINFP and TEAD2. Hsa-miR-3121-3p and hsa-miR-495-3p were the most important microRNAs (miRNAs) associated with both disorders. Finally, our study predicted 19 existing drugs (importantly, Haloperidol, Fluoxetine and Melatonin) that may have a potential influence on this co-occurrence. To summarize, this study may help us to better understand and handle the co-occurrence of SCZ and OCD by identifying potential biomarkers and therapeutic targets.

Obsessive-compulsive disorder (OCD) is characterized by recurrent distressing thoughts and repetitive behaviors, or mental rituals performed to reduce anxiety. Recent neurobiological techniques have been particularly convincing in suggesting that cortico-striatal-thalamic-cortico (CSTC) circuits, including orbitofrontal cortex (OFC) and striatum regions (caudate nucleus and putamen), are responsible for mediation of OCD symptoms. However, it is still unclear how these regions are affected by OCD treatments in adult patients. To address this yet open question, we conducted a systematic review of all studies examining neurobiological changes before and after first-line psychological OCD treatment, i.e., cognitive-behavioral therapy (CBT).

Studies were included if they were conducted in adults with OCD and they assessed the neurobiological effects of CBT before and after treatment. Two databases were searched: PsycINFO and PubMed for the time frame up to May 2022.

We obtained 26 pre-post CBT treatment studies performed using different neurobiological techniques, namely functional magnetic resonance imaging (fMRI), Positron emission tomography (PET), regional cerebral blood flow (rCBF), 5-HT concentration, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), Electroencephalography (EEG). Neurobiological data show the following after CBT intervention: (i) reduced activations in OFC across fMRI, EEG, and rCBF; (ii) decreased activity in striatum regions across fMRI, rCBF, PET, and MRI; (iii) increased activations in cerebellum (CER) across fMRI and MRI; (iv) enhanced neurochemical concentrations in MRS studies in OFC, anterior cingulate cortex (ACC) and striatum regions. Most of these neurobiological changes are also accompanied by an improvement in symptom severity as assessed by a reduction in the Y-BOCS scores.

Cognitive-behavioral therapy seems to be able to restructure, modify, and transform the neurobiological component of OCD, in addition to the clinical symptoms. Nevertheless, further studies are necessary to frame the OCD spectrum in a dimensional way.