Heart rate and heart rate variability in obsessive-compulsive disorder: Evidence from patients and unaffected first-degree relatives.

Altered heart rate (HR) and heart rate variability (HRV) are common observations in psychiatric disorders. Yet, few studies have examined these cardiac measures in obsessive-compulsive disorder (OCD). The current study aimed to investigate HR and HRV, indexed by the root mean square of successive differences (RMSSD) and further time domain indices, as putative biological characteristics of OCD. Electrocardiogram was recorded during a five-minute resting state. Group differences between patients with OCD (n = 96), healthy participants (n = 112), and unaffected first-degree relatives of patients with OCD (n = 47) were analyzed. As potential moderators of group differences, we examined the influence of age and medication, respectively. As results indicated, patients with OCD showed higher HR and lower HRV compared to healthy participants. These group differences were not moderated by age. Importantly, subgroup analyses showed that only medicated patients displayed lower HRV compared to healthy individuals, while HR alterations were evident in unmedicated patients. Regarding unaffected first-degree relatives, group differences in HRV remained at trend level. Further, an age-moderated group differentiation showed that higher HRV distinguished relatives from healthy individuals in young adulthood, whereas at higher age lower HRV was indicative of relatives. Both the role of familial risk and medication in HRV alterations need further elucidation. Pending future studies, alterations in HR and potentially HRV might serve as useful indices to characterize the pathophysiology of OCD.

White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group.

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response.

Obsessive-compulsive disorder (OCD) is a prevalent mental disorder affecting ~2-3% of the population. This disorder involves genetic and, possibly, epigenetic risk factors. The dynamic nature of epigenetics also presents a promising avenue for identifying biomarkers associated with symptom severity, clinical progression, and treatment response in OCD. We, therefore, conducted a comprehensive case-control investigation using Illumina MethylationEPIC BeadChip, encompassing 185 OCD patients and 199 controls recruited from two distinct sites in Germany. Rigorous clinical assessments were performed by trained raters employing the Structured Clinical Interview for DSM-IV (SCID-I). We performed a robust two-step epigenome-wide association study that led to the identification of 305 differentially methylated CpG positions. Next, we validated these findings by pinpointing the optimal set of CpGs that could effectively classify individuals into their respective groups. This approach identified a subset comprising 12 CpGs that overlapped with the 305 CpGs identified in our EWAS. These 12 CpGs are close to or in genes associated with the sweet-compulsive brain hypothesis which proposes that aberrant dopaminergic transmission in the striatum may impair insulin signaling sensitivity among OCD patients. We replicated three of the 12 CpGs signals from a recent independent study conducted on the Han Chinese population, underscoring also the cross-cultural relevance of our findings. In conclusion, our study further supports the involvement of epigenetic mechanisms in the pathogenesis of OCD. By elucidating the underlying molecular alterations associated with OCD, our study contributes to advancing our understanding of this complex disorder and may ultimately improve clinical outcomes for affected individuals.

Don't worry, it won't be fine. Contributions of worry and anxious arousal to startle responses and event-related potentials in threat anticipation.

A widely shared framework suggests that anxiety maps onto two dimensions: anxious apprehension and anxious arousal. Previous research linked individual differences in these dimensions to differential neural response patterns in neuropsychological, imaging, and physiological studies. Differential effects of the anxiety dimensions might contribute to inconsistencies in prior studies that examined neural processes underlying anxiety, such as hypersensitivity to unpredictable threat. We investigated the association between trait worry (as a key component of anxious apprehension), anxious arousal, and the neural processing of anticipated threat. From a large online community sample (N = 1,603), we invited 136 participants with converging and diverging worry and anxious arousal profiles into the laboratory. Participants underwent the NPU-threat test with alternating phases of unpredictable threat, predictable threat, and safety, while physiological responses (startle reflex and startle probe locked event-related potential components N1 and P3) were recorded. Worry was associated with increased startle responses to unpredictable threat and increased attentional allocation (P3) to startle probes in predictable threat anticipation. Anxious arousal was associated with increased startle and N1 in unpredictable threat anticipation. These results suggest that trait variations in the anxiety dimensions shape the dynamics of neural processing of threat. Specifically, trait worry seems to simultaneously increase automatic defensive preparation during unpredictable threat and increase attentional responding to threat-irrelevant stimuli during predictable threat anticipation. The current study highlights the utility of anxiety dimensions to understand how physiological responses during threat anticipation are altered in anxiety and supports that worry is associated with hypersensitivity to unpredictable, aversive contexts.

Affective evaluation of errors and neural error processing in obsessive-compulsive disorder.

Even though overactive error monitoring, indexed by enhanced amplitudes of the error-related negativity (ERN), is a potential biomarker for obsessive-compulsive disorder (OCD), the mechanisms underlying clinical variations in ERN amplitude remain unknown. To investigate whether ERN enhancement in OCD results from altered error evaluation, we examined the trial-wise valence evaluation of errors and its relation to the ERN in 28 patients with OCD and 28 healthy individuals. Electroencephalogram was recorded during an affective priming paradigm in which responses in a go/no-go task were followed by valence-based word categorization. Results indicated that errors were followed by faster categorization of negative than positive words, confirming that negative valence is assigned to errors. This affective priming effect was reduced in patients with OCD, while go/no-go performance was comparable between groups. Notably, this reduction amplified with increasing symptom severity. These results suggest attenuated affective error evaluation in OCD, possibly resulting from interfering effects of anxiety. There was no evidence for a trial-level association between valence evaluation and ERN, implying that ERN amplitude does not reflect valence assignment to errors. Consequently, altered error monitoring in OCD may involve alterations in possibly distinct processes, with weaker assignment of negative valence to errors being one of them.

Lack of speeded disengagement from facial expressions of disgust in remitted major depressive disorder: Evidence from an eye-movement study.

Acute major depression is characterized by specific abnormalities in the way emotional material is attended to. In late stages of stimulus processing, clinically depressed and dysphoric individuals show difficulties to disengage attention from emotionally negative material. It is unclear, however, whether aberrant disengagement is a transitory attentional phenomenon tied to depressive symptoms, or whether it constitutes a more stable disposition that outlast the symptomatic episode. To address this issue, the current study examined 39 currently euthymic individuals previously affected by major depression (RMD) and 40 healthy control participants reporting no lifetime psychopathology (ND). We used a gaze-contingent eye tracking paradigm designed to separately assess the attentional components of engagement and disengagement when viewing facial expressions of sadness, disgust and happiness. Never-depressed healthy participants, but not remitted euthymic individuals, showed speeded disengagement from facial expressions of disgust. We propose that the lack of this distinct acceleration in previously depressed but fully remitted individuals might reflect an attentional disposition that carries over to euthymic phases of the disease. On the other hand, a tendency to disengage quickly from areas in the visual field that convey social disdain could potentially act as a protective, possibly mood-stabilizing bias in resilient individuals.

Associations of neural error-processing with symptoms and traits in a dimensional sample recruited across the obsessive-compulsive spectrum.

The error-related negativity (ERN), a neural response to errors, has been associated with several forms of psychopathology and assumed to represent a neural risk marker for obsessive-compulsive disorder (OCD) and anxiety disorders. Yet, it is still unknown which specific symptoms or traits best explain ERN variation. This study investigated performance-monitoring in participants (N = 100) recruited across a spectrum of obsessive-compulsive characteristics (n = 26 patients with OCD; n = 74 healthy participants including n = 24 with low, n = 24 with medium, and n = 26 with high OC-characteristics). Several compulsivity- and anxiety-associated characteristics were assessed and submitted to exploratory principal axis factor analysis. Associations of raw measures and derived factors with ERN and correct-related negativity (CRN) were examined. Patients with OCD showed increased ERN amplitudes compared to healthy participants. The ERN was associated with a variety of traits related to anxiety and negative affect. Factor analysis results revealed a most prominent association of the ERN with a composite measure of anxiety and neuroticism, whereas the CRN was specifically associated with compulsivity. Results support differential associations for the ERN and CRN and demonstrate that a dimensional recruitment approach and use of composite measures can improve our understanding of characteristics underlying variation in neural performance monitoring.

Effects of a three-week executive control training on adaptation to task difficulty and emotional interference.

Intact executive functions are characterized by flexible adaptation to task requirements, while these effects are reduced in internalizing disorders. Furthermore, as executive functions play an important role in emotion regulation, deficits in executive functions may contribute to symptom generation in psychological disorders through increased emotional interference. Thus, the present study investigated transfer effects of a three-week executive control training on adaptation to task difficulty and emotional interference in healthy participants (n = 24) to further explore the training's suitability for clinical application. To assess the adaptation to task difficulty, the proportion congruency effect on behavioral data (response times, error rates) and ERP measures (N2, CRN) was assessed in a flanker task with varying frequency of incompatible trials (25%, 75%). To quantify emotional interference, flanker stimuli were superimposed on neutral or negative pictures. Replicating previous results, the training increased interference control as indexed by decreased response times and errors rates, increased N2 amplitude and decreased CRN amplitude in incompatible trials after training. Proportion congruency effects were weaker than expected and not affected by the training intervention. The training lead to a shift in the time-point of emotional interference: before training negative pictures lead to a reduction in CRN amplitude, while after training this reduction was observed for the N2. This pattern illustrates that the training leads to a change in task processing mode from predominant response-related cognitive control to predominant stimulus-related cognitive control (N2), indicating a proactive processing mode.

Error-Related Brain Activity in Patients With Obsessive-Compulsive Disorder and Unaffected First-Degree Relatives: Evidence for Protective Patterns.

Background: Indicators of increased error monitoring are associated with obsessive-compulsive disorder (OCD), as shown in electroencephalography and functional magnetic resonance imaging studies. As most studies used strictly controlled samples (excluding comorbidity and medication), it remains open whether these findings extend to naturalistic settings. Thus, we assessed error-related brain activity in a large, naturalistic OCD sample. We also explored which activity patterns might qualify as vulnerability endophenotypes or protective factors for the disorder. To this aim, a sample of unaffected first-degree relatives of patients with OCD was also included. Methods: Participants (84 patients with OCD, 99 healthy control participants, and 37 unaffected first-degree relatives of patients with OCD) completed a flanker task while blood oxygen level-dependent responses were measured with functional magnetic resonance imaging. Aberrant error-related brain activity in patients and relatives was identified. Results: Patients with OCD showed increased error-related activity in the supplementary motor area and within the default mode network, specifically in the precuneus and postcentral gyrus. Unaffected first-degree relatives showed increased error-related activity in the bilateral inferior frontal gyrus. Conclusions: Increased supplementary motor area and default mode network activity in patients with OCD replicates previous studies and might indicate excessive error signals and increased self-referential error processing. Increased activity of the inferior frontal gyrus in relatives may reflect increased inhibition. Impaired response inhibition in OCD has been demonstrated in several studies and might contribute to impairments in suppressing compulsive actions. Thus, increased inferior frontal gyrus activity in the unaffected relatives of patients with OCD may have contributed to protection from symptom development.

Error-related activity of the sensorimotor network contributes to the prediction of response to cognitive-behavioral therapy in obsessive-compulsive disorder.

BACKGROUND: Although cognitive behavioral therapy is a highly effective treatment for obsessive-compulsive disorder (OCD), yielding large symptom reductions on the group level, individual treatment response varies considerably. Identification of treatment response predictors may provide important information for maximizing individual treatment response and thus achieving efficient treatment resource allocation. Here, we investigated the predictive value of previously identified biomarkers of OCD, namely the error-related activity of the supplementary motor area (SMA) and the sensorimotor network (SMN, postcentral gyrus/precuneus). METHODS: Seventy-two participants with a primary diagnosis of OCD underwent functional magnetic resonance imaging (fMRI) scanning while performing a flanker task prior to receiving routine-care CBT. RESULTS: Error-related BOLD response of the SMN significantly contributed to the prediction of treatment response beyond the variance accounted for by clinical and sociodemographic variables. Stronger error-related SMN activity at baseline was associated with a higher likelihood of treatment response. CONCLUSIONS: The present results illustrate that the inclusion of error-related SMN activity can significantly increase treatment response prediction quality in OCD. Stronger error-related activity of the SMN may reflect the ability to activate symptom-relevant processing networks and may thus facilitate response to exposure-based CBT interventions.

Early hypervigilance and later avoidance: Event-related potentials track the processing of threatening stimuli in anxiety.

Avoidance behavior is a core symptom of anxiety disorders that may hinder adaptation. Anxiety disorders are heterogeneous and previous research suggests to decompose anxiety into two dimensions: anxious apprehension and anxious arousal. How these two dimensions are associated with avoidance of and exposure to threatening stimuli, as well as their accompanying neural processes, is barely understood. We examined threat processing using event-related potentials (N1, LPP) from 134 individuals considering the influence of anxiety dimensions. During a two-phase picture-viewing task the participants watched neutral and threatening pictures, which they were instructed to either avoid or attend to during repeated presentations. Results showed that threatening compared to neutral pictures were associated with increased attention allocation (N1) and in-depth processing (LPP), modulated by task-instructions (lower during avoidance). Further, increased anxious apprehension was associated with heightened automatic attention (increased N1), followed by reduced LPP amplitudes for threatening pictures suggesting reduced in-depth processing. During re-exposure, threatening pictures were associated with increased in-depth processing, with no difference between previously avoided and maintained pictures. Together, these results illustrate that avoidance and high anxious apprehension seem to lead to similar neural changes in the processing of aversive images that may conflict with long-term adaptation.

Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium.

BACKGROUND: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. METHODS: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6-65) was divided into six successive 6-10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. RESULTS: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6-13 and adults aged 50-65 with OCD taking SRIs (Cohen's d = -0.24 to -0.74). Volumes of putamen, pallidum (d = 0.18-0.40), and ventricles (d = 0.31-0.66) were greater in patients aged 20-29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = -0.27 to -1.31). CONCLUSIONS: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20-29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

Non-invasive brain stimulation modulates neural correlates of performance monitoring in patients with obsessive-compulsive disorder.

Overactive performance monitoring, as reflected by enhanced neural responses to errors (the error-related negativity, ERN), is considered a biomarker for obsessive-compulsive disorder (OCD) and may be a promising target for novel treatment approaches. Prior research suggests that non-invasive brain stimulation with transcranial direct current stimulation (tDCS) may reduce the ERN in healthy individuals, yet no study has investigated its efficacy in attenuating the ERN in OCD. In this preregistered, randomized, sham-controlled, crossover study, we investigated effects of tDCS on performance monitoring in patients with OCD (n = 28) and healthy individuals (n = 28). Cathodal and sham tDCS was applied over the presupplementary motor area (pre-SMA) in two sessions, each followed by electroencephalogram recording during a flanker task. Cathodal tDCS reduced the ERN amplitude compared to sham tDCS, albeit this effect was only marginally significant (p = .052; mean difference: 0.86 µV). Additionally, cathodal tDCS reduced the correct-response negativity and increased the error positivity. These neural modulations were not accompanied by behavioral changes. Moreover, we found no evidence that the tDCS effect was more pronounced in the patient group. In summary, our findings indicate that tDCS over the pre-SMA modulates neural correlates of performance monitoring across groups. Therefore, this study represents a valuable starting point for future research to determine whether repeated tDCS application induces a more pronounced ERN attenuation and normalizes aberrant performance monitoring in the long term, thereby potentially alleviating obsessive-compulsive symptoms and providing a psychophysiological intervention strategy for individuals who do not benefit sufficiently from existing interventions.

[Treatment of obsessive-compulsive disorders: recommendations of the revised S3 guidelines on obsessive-compulsive disorders]. / Therapie der Zwangsstörungen: Empfehlungen der revidierten S3-Leitlinie Zwangsstörungen.

In 2022, the first revised version of the S3 guidelines on obsessive-compulsive disorder will be published under the auspices of the German Society for Psychiatry, Psychotherapy and Psychosomatics (DGPPN). This article contains a summary of the most important recommendations for therapy in a condensed form. There were no major changes in the central basic therapy recommendations compared with the first version of the guidelines, as the evidence base has not fundamentally changed since then. Cognitive behavioral therapy (CBT) with exposure and response management is the most effective form of therapy for this clinical picture and therefore the therapy of first choice. Regarding pharmacotherapy, selective serotonin reuptake inhibitors are the first-line medications. They are indicated when CBT with exposure is not available or has not been effective, when CBT is rejected by the patient and in the patient's personal preference for medication, or to increase the readiness for CBT with exposure. New recommendations include, e.g., the use of Internet therapy, and recommendations for the use of CBT and exposure, e.g., also in group format, including video conferencing if appropriate as well as in intensive format.

Neural correlates of emotional reactivity predict response to cognitive-behavioral therapy in obsessive-compulsive disorder.

BACKGROUND: Examining predictive biomarkers to identify individuals who will likely benefit from a specific treatment is important for the development of targeted interventions. The late positive potential (LPP) is a neural marker of attention and elaborated stimulus processing, and increased LPP responses to negative stimuli are characteristic of pathological anxiety. The present study investigated whether LPP reactivity would prospectively predict response to cognitive-behavioral therapy (CBT), the first-line treatment for obsessive-compulsive disorder (OCD). METHODS: To this end, the LPP in response to negative as compared to neutral pictures was examined in 45 patients with OCD, who underwent CBT in a naturalistic outpatient setting. LPP amplitudes were used as predictors of symptom reduction after CBT. RESULTS: We found that higher LPP amplitudes to negative relative to neutral stimuli were predictive of lower self-reported OCD symptoms after completion of CBT, controlling for pre-treatment symptoms. Further, LPP reactivity was negatively correlated with self-reported habitual use of suppression in everyday life. LIMITATIONS: Some participants had already begun treatment at the time of study participation. Overall, results need further replication in larger samples and standardized therapy settings. CONCLUSIONS: The current findings suggest that patients with increased emotional reactivity benefit more from CBT, possibly through less avoidance of anxiety-provoking stimuli during exposure with response prevention, a crucial component in CBT for OCD. Although its clinical utility still needs to be evaluated further, the LPP constitutes a promising candidate as a prognostic marker for CBT response in OCD.

The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder.

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.

Exposure to childhood maltreatment and systemic inflammation across pregnancy: The moderating role of depressive symptomatology.

BACKGROUND: Childhood maltreatment (CM) has long-term consequences for dysregulation of the immune system which is particularly pronounced when mental and physical health sequelae have manifested. Higher proinflammatory state has been shown in non-pregnant state in association with CM as well as with depression, one of the most frequent and pernicious psychiatric sequelae of CM. During pregnancy, however, this association is less clear. Given the important role of maternal inflammatory state during pregnancy for fetal, pregnancy, and birth outcomes, we sought to examine the association between CM and proinflammatory state during pregnancy considering the moderating role of maternal depressive symptoms characterized serially across pregnancy. METHODS: A prospective, longitudinal study of 180 healthy pregnant women was conducted with serial assessments in early (12.98 ± 1.71 weeks gestation), mid (20.53 ± 1.38 weeks gestation) and late (30.42 ± 1.4 weeks gestation) pregnancy. Maternal history of CM was assessed with the Childhood Trauma Questionnaire (CTQ) and the total score was used as an indicator of CM experience. Maternal depressive symptoms were assessed at each pregnancy visit with the Center for Epidemiologic Studies Depression Scale (CES-D). Serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were obtained at each pregnancy visit and combined to a composite maternal proinflammatory score. Linear mixed effects models were employed to assess the association between CTQ score, CES-D score, and proinflammatory score during pregnancy, adjusting for potential confounders. RESULTS: Gestational age was associated with the proinflammatory score (B = 0.02; SE = 0.00; p < .001), indicating an increase in inflammation across gestation. Neither CTQ score nor depressive symptoms were independently associated with the proinflammatory score (ps > 0.28). However, the interaction between CTQ score and depressive symptoms was associated with the proinflammatory score (B = 0.03, SE = 0.01, p < .05), indicating higher inflammation across pregnancy with increasing levels of depressive symptoms during pregnancy in women with higher CTQ scores. Exploratory analyses suggested that this interaction was mainly driven by CTQ subscale scores assessing experiences of abuse rather than neglect. CONCLUSIONS: These findings suggest a moderating role of maternal depressive symptoms during pregnancy on the association of early life stress with inflammation and thus highlight the importance of the timely assessment of both CM exposure and depressive symptoms which might allow for the development of targeted and individualized interventions to impact inflammation during pregnancy and to ameliorate the detrimental long-term effects of CM. The current findings add to a better understanding of the prenatal biological pathways that may underlie intergenerational transmission of maternal CM.

Effectiveness of Individual Cognitive-Behavioral Therapy and Predictors of Outcome in Adult Patients with Obsessive-Compulsive Disorder.

INTRODUCTION: Cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) has proven its efficacy in randomized controlled trials (RCTs). OBJECTIVE: To test generalizability to routine care settings, we conducted an effectiveness study to provide naturalistic outcome data and their predictors. METHODS: Pre-post changes in symptoms and impairment as well as response rates were determined in a naturalistic OCD sample (intention-to-treat, ITT, n = 393). Patients received individual CBT for OCD adopting an exposure-based, non-manualized treatment format. Linear and logistic regression analyses were applied to identify associations of sociodemographic and clinical variables with symptom change. RESULTS: Effect size in ITT patients amounted to d = 1.47 in primary outcome (Yale-Brown Obsessive-Compulsive Scale, Y-BOCS). Remission rates were 46.3% (ITT), 52.0% (completers), and 18.2% (non-completers). The rates of treatment response without remission, no change, and deterioration in the ITT sample were 13.2, 38, and 3%, respectively. Initial symptom severity, comorbid personality disorder, and unemployment were associated with a poorer outcome, and previous medication with a better outcome. Comorbid depressive and anxiety disorders as well as other clinical or sociodemographic variables showed no effects on symptom change. CONCLUSIONS: Outcomes in this large observational trial in a naturalistic setting correspond to available RCT findings suggesting that CBT for OCD should be strongly recommended for dissemination in routine care. Targets for further research include early prediction of non-response and development of alternative treatment strategies for patients who respond insufficiently.