Deep brain stimulation (DBS) efficacy for psychiatric disorders remains heterogeneous due to incomplete mechanistic insights and insufficient individualized treatment planning. A biologically grounded computational framework is urgently needed to simulate DBS-related differences for treatment-resistant patients.

Resting-state fMRI data from 11 patients with obsessive-compulsive disorder (OCD) and 11 with major depressive disorder (MDD), scanned in DBS-ON and DBS-OFF states, were used to derive functional connectivity (FC) via network deconvolution. Whole-brain dynamic modeling incorporated stimulation targets, amplitudes, and frequencies to simulate DBS effects in silico.

The model recapitulated syndrome-specific DBS-related network patterns in exploratory analyses. OCD stimulation primarily altered frontal-subcortical connectivity, whereas MDD stimulation predominantly affected default mode network hubs (p < 0.05). Under leave-one-out cross-validation, correlations between predicted and observed clinical outcomes were r = 0.625 in OCD (p = 0.040) and r = 0.659 in MDD (p = 0.028). Applying the same FC signatures to simulated FC yielded r = 0.465 in OCD (p = 0.149) and r = 0.627 in MDD (p = 0.039). In a proof-of-concept application to a separate OCD cohort (N = 92), three individuals showed high model-predicted NAc-response profiles and predicted improvement exceeding 35%.

This hypothesis-generating framework retrospectively models DBS-related network effects using individualized resting-state FC and virtual perturbations. Linking simulated FC states with empirical DBS-ON/OFF patterns may help characterize how baseline functional architecture shapes DBS-related network responses and inform future individualized DBS modeling.

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts that are appraised as signalling harm, evoking distress and efforts to reduce distress and/or prevent harm. It has long been observed that obsessions often reflect moral themes and that many people with OCD experience strong moral emotions, particularly guilt and shame.

Drawing on social functionalist models of moral emotions and the literature on moral injury (MI), we propose that in some people with OCD, symptoms can be conceptualized as an MI.

We reviewed leading theoretical models of OCD, moral emotions, and MI, and identified areas of overlap in phenomenology, development, and persistence.

When an obsessional thought is itself a moral transgression, and/or failure to resolve the obsessional concern via the compulsion is viewed as a moral transgression, it evokes moral emotions and threatens social standing, reputation, and trust. This increases the stake in avoiding the obsession and in ensuring the compulsion is done properly.

The integration of moral injury concepts with established cognitive behavioral models may enhance case formulation, reduce treatment ambivalence, and support recovery processes that extend beyond symptom reduction to restoration of moral coherence and self-trust. Clinical implications are discussed.

Inhibitory control deficits represent a core cognitive feature in patients with obsessive-compulsive disorder (OCD), yet their neurophysiological mechanisms remain unclear. Electroencephalogram (EEG) microstates offer a novel framework for investigating large-scale brain network dynamics in psychiatric disorders. This cross-sectional study aimed to investigate EEG microstate dynamics in OCD patients and their relationships with cognitive and response inhibition.

A total of 91 OCD patients and 76 healthy controls were recruited. Participants completed an Emotional Stroop Task (EST) and a stop-signal task (SST). Resting-state EEG was recorded, and microstate parameters and transition probabilities were analyzed. Correlations between microstate parameters and inhibitory control performance were assessed.

OCD patients exhibited significant deficits in both response inhibition and cognitive inhibition, with both types of deficits positively correlated with obsessive symptom severity. Microstate analysis revealed increased mean duration and time coverage of microstate A, but decreased mean duration, occurrence, and coverage of microstate C in OCD patients. Additionally, transition probabilities from microstates B and D to C were significantly elevated. Notably, the mean duration of microstate C was positively correlated with stop-signal reaction time (SSRT), while the occurrence of microstates C and D and the time coverage of microstate D were negatively correlated with the Stroop effect.

These findings reveal dissociable microstate mechanisms associated with distinct inhibitory dysfunction domains in OCD patients. Resting-state microstate dynamics may represent candidate neurobiological markers for cognitive subtype classification in OCD and may help inform the development of targeted therapeutic interventions.

Cognitive fusion (CF), a core maladaptive process in obsessive-compulsive disorder (OCD), describes overidentification with intrusive thoughts. While implicated in symptom maintenance, its neuroanatomical basis and treatment prediction utility remain poorly understood.

We enrolled 80 first-episode, drug-naïve OCD patients and 70 matched healthy controls. All participants underwent structural magnetic resonance imaging and clinical assessment. Patients received 8-week selective serotonin reuptake inhibitors treatment with endpoint reevaluation. Using multimodal neuroimaging, we examined group differences in gray matter volume (GMV) and structural covariance network (SCN), tested whether CF levels modulated connectivity, and evaluated baseline features for predicting treatment response. Transcriptomic analysis linked the findings to the Allen Human Brain Atlas data.

OCD patients showed GMV reductions in frontal-limbic regions and increases in parietal/inferior frontal areas. SCN analysis revealed enhanced structural covariance within fronto-parieto-cerebellar circuits. Higher CF scores were associated with stronger structural coupling between the left angular gyrus and the right middle temporal/medial superior frontal gyri. Baseline GMV in the left dorsolateral superior frontal gyrus (SFGdl) positively correlated with CF improvement, remaining significant after controlling for overall symptom reduction. Transcriptomic analysis indicated the left SFGdl GMV patterns spatially associated with glutamatergic synapse and calcium signaling pathways.

CF in OCD links to altered structural integration between large-scale networks, with the left SFGdl emerging as a potential CF-specific treatment predictor. This multiscale study highlights combining neuroimaging with psychological constructs to understand treatment-relevant changes in OCD.

Associations between childhood streptococcal upper respiratory infections and subsequent psychiatric outcomes have been described for over 25 years, although clinical evidence remains limited. This study explored psychiatric outcomes after pediatric streptococcal versus non-streptococcal upper respiratory tract infections.

This retrospective cohort study used TriNetX, a global federated health research network of over 150 million deidentified electronic medical records. We compared children aged 3–16 with a diagnosis of acute upper respiratory infection (ICD-10 J00-J06) and a Streptococcus pyogenes test result (positive or negative) within 2 weeks, propensity matched on 70 baseline variables. Main outcomes were the 1-year incidence of any psychiatric disorder, obsessive-compulsive disorder (OCD), tic disorder, anxiety, and restricted oral intake.

Before matching, 464,513 children were streptococcal positive and 1,023,171 children were streptococcal negative. After matching, there were 456,221 children in each cohort (48% female). The streptococcal-positive cohort had a reduced risk of any psychiatric disorder (RR 0.92 [0.90, 0.94]), restricted oral intake (0.81 [0.77, 0.86]), and anxiety disorder (0.94 [0.91, 0.97]) at 1 year. Risk of OCD (RR 0.98 [0.86, 1.12]) and tic disorder (RR 0.95 [0.87, 1.04]) was not significantly different between the two cohorts.

This large-scale cohort study found no evidence that exposure to S. pyogenes is associated with increased risk of the measured psychiatric outcomes.

Gambling disorder frequently co-occurs with other psychiatric conditions, yet its relationship with obsessive-compulsive disorder (OCD) remains unclear. Emerging evidence suggests impulsivity and compulsivity may be inter-related rather than diametrically opposed constructs, warranting investigation of their clinical overlap. The aim of this study is to examine the rate of gambling disorder in adults with OCD and to explore associated clinical, behavioral, and treatment-related characteristics.

Adults with probable OCD were recruited via online Reddit groups for OCD, OCD clinics, and support groups and completed a cross-sectional survey. OCD symptom types were assessed using the Obsessive-Compulsive Inventory-Revised, and gambling disorder was identified using the Minnesota Impulsive Disorders Interview. Additional measures included gambling severity, impulsivity, and problematic internet use. Group comparisons were conducted between participants with and without gambling disorder.

Among 186 adults with OCD, 34 (18.8%) met criteria for gambling disorder. Individuals with comorbid gambling disorder demonstrated significantly greater OCD severity, particularly in ordering, checking, and neutralizing symptoms, and reported later onset of OCD. The comorbid group showed higher impulsivity, greater problematic internet use, and distinct gambling behaviors, including higher rates of online gambling, esports betting, and use of artificial intelligence tools for gambling. They were also less likely to have received pharmacological treatment for OCD.

Gambling disorder in adults with OCD is associated with distinct clinical characteristics, greater impulsivity, problematic internet use, and concerning treatment gaps. These findings highlight the importance of screening for gambling in OCD, and vice versa, and suggest a need for integrated treatment approaches.

It is unclear whether patients with obsessive-compulsive disorder (OCD) and expert clinicians agree on the symptoms’ qualities that are essential for a diagnosis of OCD. This study examined whether OCD patients and expert clinicians agree on the essential characteristics for an OCD diagnosis. It compared the endorsement rates of various descriptive terms and assessed whether response profiles could predict group membership (patients versus expert clinicians).

Sixty-four OCD patients and 36 OCD expert clinicians answered a questionnaire on their views regarding the defining characteristics of OCD symptoms. It included a compilation of adjectives extracted from DSM-5 to describe disorders in the compulsive–impulsive spectrum. Chi-square tests compared response prevalence between groups and binary regression identified distinguishing features. The significance level was set at 0.05.

All descriptors differed significantly between OCD patients and expert clinicians (p < 0.01), with clinicians consistently endorsing more items as applicable or essential. Although the logistic regression model significantly distinguished the 2 groups and showed high explanatory power (R2 = 0.7) with 99% classification accuracy, no individual descriptors were significant predictors.

There is a mismatch between clinician-defined diagnostic language and patients’ subjective experience of OCD, including core symptom descriptors. This gap suggests that current OCD diagnostic construct may not fully capture how patients perceive their condition, potentially limiting its validity and clinical utility. Adopting more patient-centered language could improve assessment, psychoeducation, and treatment engagement.

The term ‘schizo-obsessive comorbidity (SOC)’ is used to describe the presence of obsessive-compulsive symptoms or obsessive-compulsive disorder (OCD) in patients with schizophrenia (SOC). Recent studies have found overlapped executive dysfunctions in SCZ and OCD implicating shared pathophysiology. However, specific deficits in the components of executive function (EF) in patients with SOC remains unclear.

We recruited 37 patients with SOC, 68 patients with SCZ, 70 patients with OCD, and 59 healthy controls (HCs). All participants completed a battery of measures for EF components, namely initiation, sustained attention, online updating, switching, disinhibition, and planning. Apart from traditional group-mean analysis, we applied machine learning approaches to identify the unique patterns of EF among different clinical groups.

The results showed that the three clinical groups could be distinguished from HCs. The feature importance analysis showed that, to classify clinical groups from HC, online updating was the core feature of SCZ patients, whereas disinhibition and online updating jointly determine classification between OCD patients and HC. In differentiating SOC from HC, online updating, planning, and disinhibition collectively served as key features. Machine learning algorithms classified SOC and OCD with acceptable performance but classified SOC and SCZ with lower performance.

Deficits of EF are shared features among patients with SOC, SCZ, and OCD. However, the specific components of executive dysfunction in these clinical groups appeared distinct.

The network theory of mental disorders posits that associations between symptoms activate other symptoms to maintain a disorder over time. Network analytic approaches therefore may inform treatment targets. In the present study, we compared baseline OCD symptom networks among treatment responders to non-responders and examined how network structure and connectivity changed from before to after exposure and response prevention (ERP) treatment.

Community adults with OCD (n = 712) who underwent intensive outpatient treatment were assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS) at admission and discharge. Network comparison tests were used to (a) examine differences in baseline symptom network structures between treatment responders versus non-responders and (b) examine changes in network structures from pre- to post-treatment.

Pre-treatment network structures and global connectivity did not differ significantly between treatment responders and non-responders. However, post-treatment networks exhibited greater global strength (i.e., stronger associations between OCD symptoms) and significantly different network structure (i.e., different patterns of associations between OCD symptoms) relative to the pre-treatment network.

Findings showed that network structure and connectivity in OCD may be more informative as a marker of therapeutic change than in discriminating treatment responders from nonresponders using baseline symptoms. After ERP treatment, associations between obsessions and compulsions demonstrated significantly greater global network strength and altered network structure, thus underscoring the potential for network approaches to identify mechanisms of change throughout OCD treatment. Future studies incorporating session-by-session data may clarify when and how these network shifts occur over the course of therapy to help identify treatment targets.

Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder characterized by recurrent intrusive thoughts and ritualized behaviors, often aimed at reducing distress. OCD is heterogeneous in its presentation and many patients with OCD experience a variety of different symptoms throughout their course of illness. Efforts to understand symptom domains in OCD have typically identified three to five symptom domains, such as the domains of doubt/checking, contamination, superstitions/rituals, symmetry/hoarding, and taboo thoughts. Recent studies in the genetics of OCD have suggested a common OCD dimension may provide additional information above and beyond the previously identified symptom domains. Thus, we sought to test a hierarchical model of lifetime OCD symptoms and evaluate the utility of the inclusion of a common OCD dimension.

Participants included 999 individuals participating in the OCD Collaborative Genetics Study (OCGS) and an additional 2363 individuals participating in the OCD Genetic Association Study (OCGAS). We evaluated unidimensional, 5-factor, and hierarchical models of lifetime OCD symptom presentation using confirmatory factor analysis.

Results suggested that the hierarchical model best fit the data. Further evaluation of these models using a Bayesian testlet response model showed that lifetime presence of specific OCD symptoms was differentially associated with lifetime OCD severity. Moreover, symptoms associated with greater lifetime severity were generally reported less frequently than symptoms present at lower levels of lifetime severity. Implications of these findings and future directions are discussed.

Although exposure and response prevention (EX/RP) is recommended as a first-line treatment for obsessive-compulsive disorder (OCD), responses vary among patients. This study was the first to use network analysis to examine how OCD symptom networks change with EX/RP and vary across different progress trajectories.

Data from four clinical trials with 334 adults with OCD who received manualized EX/RP were pooled. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was administered at baseline, midpoint, and post-treatment. OCD symptom networks were constructed using individual Y-BOCS items at these three time points, both for the entire sample and for three different progress trajectories (dramatic, moderate, and little-to-no progress) previously identified using growth mixture modeling. Network measures, including global efficiency, modularity, and weighted degree centrality, were computed to quantitatively assess network properties across treatment.

Network analysis revealed two distinct modules at baseline: resistance/control and interference/distress. In the full sample, these two modules became integrated over time, as indicated by significant increases in global efficiency and weighted degree centrality and decreases in modularity; at post-treatment, the network shifted toward a fully connected network, and the strength of associations between nodes increased. These changes were most pronounced in the dramatic progress class.

Our findings indicated that effective EX/RP treatment was associated with more integrated OCD symptom networks, which may serve as an indicator of treatment response. Future research should examine how these shifts in network connectivity correspond to changes in underlying brain circuitry and/or to early identification of treatment responders.

Studies highlight the thalamus as a key region distinguishing early- from late-onset obsessive-compulsive disorder (OCD). While structural thalamic correlates with OCD onset age are well-studied, resting-state functional connectivity (rsFC) remains largely unexplored. This study examines thalamic subregional rsFC to elucidate pathophysiological differences in OCD based on different onset times.

The study comprised 85 early-onset OCD (EO-OCD) patients, 94 late-onset OCD (LO-OCD) patients, and 94 age- and sex-matched healthy controls (HCs). rsFC analysis was conducted to assess thalamic connectivity across seven subdivisions among the groups.

Both EO-OCD and LO-OCD patients exhibited increased rsFC between the primary motor thalamus and the posterior central gyrus and between the thalamic premotor and the supplementary motor areas. EO-OCD patients showed significantly stronger rsFC between the prefrontal thalamus (Ptha) and the middle frontal gyrus (MFG) compared to both LO-OCD patients and HCs. In contrast, LO-OCD patients demonstrated reduced rsFC between the Ptha and the inferior parietal lobule (IPL) compared to EO-OCD patients and HCs. Additionally, the rsFC between the Ptha and both the MFG and IPL was negatively correlated with age of onset, with earlier onset linked to stronger connectivity.

These findings reveal both shared and distinct thalamic connectivity patterns in EO-OCD and LO-OCD patients. Sensory-motor networks exhibiting thalamic hyperconnectivity are critical for the manifestation of OCD, regardless of age of onset. The frontal–parietal network and thalamic hyperconnectivity may present a compensatory mechanism in EO-OCD patients, while hypoconnectivity with the frontoparietal network may reflect a neural mechanism underlying LO-OCD.

Obsessive-compulsive disorder (OCD) is a significantly disabling and difficult-to-treat psychiatric disorder. Non-invasive neuromodulation techniques like repetitive transcranial magnetic stimulation (rTMS) have been increasingly used in the management of OCD. This study aimed to compare the efficacy of early augmentation with low-frequency rTMS (LF-rTMS) and continuous theta burst stimulation (cTBS) in improving psychopathology in OCD patients.

The study design was a parallel-group, double-blind, randomized clinical trial. The study recruited 46 OCD patients who were randomly allocated to receive either LF-rTMS or cTBS (23 patients in each group) following the computer-generated random table method. All participants were rated on YBOCS, HAM-A, and HAM-D at baseline and third week and sixth weeks. These patients received a total of 15 sessions of LF-rTMS or cTBS stimulation once daily for 5 consecutive days in a week for 3 consecutive weeks over the right dorso-lateral pre-frontal cortex (DLPFC) area.

There was a statistically significant improvement in the total YBOCS score for both the LF-rTMS group and the cTBS group at the end of the third and sixth week when compared with their baseline scores. However, there was no statistically significant difference between the 2 groups in terms of the improvement in the total YBOCS score, as well as the total scores for the HAM-A and HAM-D during the follow-up periods.

The study results suggest that both LF-rTMS and cTBS were equally effective in managing OCD patients as an early augmentation strategy.

Bipolar disorder (BD) is commonly comorbid with other psychiatric conditions, such as obsessive-compulsive disorder (OCD). Despite increasing interest in this comorbidity, quantitative data on its clinical characteristics remain limited. This systematic review and meta-analysis aimed to evaluate the clinical impact of OCD comorbidity in BD by comparing individuals with BD and OCD (BD-OCD) to those with BD without OCD.

We systematically searched the PubMed/MEDLINE, Scopus, PsycINFO, and Web of Science databases up to April 15, 2024. Meta-analyses were conducted to compare BD-OCD and BD without OCD groups across multiple clinical domains.

From 11,959 initial records screened, 26 studies were included in the qualitative synthesis, with 22 eligible for meta-analysis. Individuals with BD-OCD showed higher odds of experiencing chronic mood episodes (OR = 9.42; 95%CI = 2.23, 39.9), rapid cycling (OR = 1.92; 95%CI = 1.04, 3.53), comorbid eating disorders (OR = 3.37; 95%CI = 1.99, 5.7), panic disorder (OR = 3.3; 95%CI = 2.11, 5.2), substance use disorders (OR = 1.39; 95%CI = 1.02, 1.89), and lifetime suicide attempts (OR = 1.85; 95%CI = 1.21, 2.84). Additionally, they presented earlier onset of BD (SMD = -0.27; 95%CI = -0.52, −0.01) and reduced functioning (SMD = -0.42; 95%CI = -0.59, −0.24). Most data were derived from adult populations, limiting the evidence available for children and adolescents.

BD-OCD presents a more severe and complex clinical profile, requiring specialized assessment and integrated treatment approaches. Identifying these features may support earlier recognition and inform personalized interventions for this population.