Abstract task sequence initiation deficit dissociates anxiety disorders from obsessive-compulsive disorder and healthy controls.

In everyday life, humans perform sequences of tasks. These tasks may be disrupted in people with obsessive-compulsive disorder (OCD). Symptoms, such as compulsions, can be considered sequential and often cause repetitions of tasks that disrupt daily living (e.g., checking the stove while cooking). Motor sequences have been used to study behavioral deficits in OCD. However, not all sequences are motor sequences. Some are more "abstract" in that they are composed of a series of tasks (e.g., chopping and stirring) rather than being dependent on individual actions or stimuli. These abstract task sequences require cognitive control mechanisms for their execution. Although theory has proposed deficits in these sequences in OCD as well, they have not been directly investigated. We tested the hypotheses that OCD participants exhibit deficits in the control mechanisms specific to abstract task sequences and more general flexible behavior (measured with task switching within the sequences), relative to health controls (HCs) and clinical controls (participants with anxiety disorders [ANX]). A total of 112 participants completed abstract task sequences consisting of simple categorization tasks. Surprisingly, participants with OCD did not perform worse than HCs or ANX. However, ANX participants showed impairments specific to sequential control that did not extend to more general flexible control. Thus, we showed a novel behavioral dissociation between OCD and ANX specific to abstract task sequential control. These results also implicate deficits in specific frontal sequential control neural circuitry in ANX and not in OCD, where implicit sequential deficits may more closely align with striatal circuits.

Impact of the peripartum period on the longitudinal course of obsessive-compulsive disorder.

Some women are vulnerable to developing new onset obsessive-compulsive disorder (OCD) or having an exacerbation of pre-existing OCD during reproductive cycle events. Reports on the impact of the peripartum period on pre-existing OCD are inconsistent, with both worsening and improving symptom severity described. Studies have primarily been retrospective or have collected few data points, which limits the investigators' ability to capture the range of OCD symptoms during this time period, systematically and prospectively. The objective of this investigation was to add to the existing literature on the impact of the peripartum period on the course of pre-existing OCD. We conducted a secondary analysis of a subset data from the Brown Longitudinal Obsessive Compulsive Study, a prospective, observational study of OCD course. Nineteen women who experienced a pregnancy during the course of the study (9.5% of overall sample of women) were followed on average for 486 ± 133 weeks. Weekly psychiatric status ratings (PSRs) of OCD severity were compared between peripartum and non-peripartum periods. We found that the peripartum period did not significantly impact the course of OCD severity in the majority of women (N = 13, 69%). Of the minority of women with measurable variability in OCD symptoms, no statistically significant difference in PSR scores was observed between peripartum and non-peripartum periods. In this novel yet small dataset, the severity of OCD does not appear to worsen for most women during the peripartum period.

Trichotillomania comorbidity in a sample enriched for familial obsessive-compulsive disorder.

BACKGROUND: This study addresses the strength of associations between trichotillomania (TTM) and other DSM-IV Axis I conditions in a large sample (n = 2606) enriched for familial obsessive-compulsive disorder (OCD), to inform TTM classification. METHODS: We identified participants with TTM in the Johns Hopkins OCD Family Study (153 families) and the OCD Collaborative Genetics Study, a six-site genetic linkage study of OCD (487 families). We used logistic regression (with generalized estimating equations) to assess the strength of associations between TTM and other DSM-IV disorders. RESULTS: TTM had excess comorbidity with a number of conditions from different DSM-IV chapters, including tic disorders, alcohol dependence, mood disorders, anxiety disorders, impulse-control disorders, and bulimia nervosa. However, association strengths (odds ratios) were highest for kleptomania (6.6), pyromania (5.8), OCD (5.6), skin picking disorder (4.4), bulimia nervosa (3.5), and pathological nail biting (3.4). CONCLUSIONS: TTM is comorbid with a number of psychiatric conditions besides OCD, and it is strongly associated with other conditions involving impaired impulse control. Though DSM-5 includes TTM as an OCD-related disorder, its comorbidity pattern also emphasizes the impulsive, appetitive aspects of this condition that may be relevant to classification.

Self-reported executive function and hoarding in adults with obsessive-compulsive disorder.

BACKGROUND: Hoarding behavior may distinguish a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Little is known about the relationship between executive dysfunction and hoarding in individuals with OCD. METHODS: The study sample included 431 adults diagnosed with DSM-IV OCD. Participants were assessed by clinicians for Axis I disorders, personality disorders, indecision, and hoarding. Executive functioning domains were evaluated using a self-report instrument, the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). We compared scores on these domains in the 143 hoarding and 288 non-hoarding participants, separately in men and women. We used logistic regression to evaluate relationships between executive function scores and hoarding, and correlation and linear regression analyses to evaluate relationships between executive function scores and hoarding severity, in women. RESULTS: In men, the hoarding group had a significantly higher mean score than the non-hoarding group only on the shift dimension. In contrast, in women, the hoarding group had higher mean scores on the shift scale and all metacognition dimensions, i.e., those that assess the ability to systematically solve problems via planning and organization. The relationships in women between hoarding and scores on initiating tasks, planning/organizing, organization of materials, and the metacognition index were independent of other clinical features. Furthermore, the severity of hoarding in women correlated most strongly with metacognition dimensions. CONCLUSIONS: Self-reported deficits in planning and organization are associated with the occurrence and severity of hoarding in women, but not men, with OCD. This may have implications for elucidating the etiology of, and developing effective treatments for, hoarding in OCD.

Parental bonding and hoarding in obsessive-compulsive disorder.

BACKGROUND: Hoarding behavior may indicate a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Empirical evidence supports a relationship between hoarding and emotional over-attachment to objects. However, little is known about the relationship between hoarding and parental attachment in OCD. METHOD: The study sample included 894 adults diagnosed with DSM-IV OCD who had participated in family and genetic studies of OCD. Participants were assessed for Axis I disorders, personality disorders, and general personality dimensions. The Parental Bonding Instrument (PBI) was used to assess dimensions of perceived parental rearing (care, overprotection, and control). We compared parental PBI scores in the 334 hoarding and 560 non-hoarding participants, separately in men and women. We used logistic regression to evaluate the relationship between parenting scores and hoarding in women, adjusting for other clinical features associated with hoarding. RESULTS: In men, there were no significant differences between hoarding and non-hoarding groups in maternal or paternal parenting scores. In women, the hoarding group had a lower mean score on maternal care (23.4 vs. 25.7, p<0.01); a higher mean score on maternal protection (9.4 vs. 7.7, p<0.001); and a higher mean score on maternal control (7.0 vs. 6.2, p<0.05), compared to the non-hoarding group. The magnitude of the relationships between maternal bonding dimensions and hoarding in women did not change after adjustment for other clinical features. Women who reported low maternal care/high maternal protection had significantly greater odds of hoarding compared to women with high maternal care/low maternal protection (OR=2.54, 95% CI=1.60-4.02, p<0.001). CONCLUSIONS: Perceived poor maternal care, maternal overprotection, and maternal overcontrol are associated with hoarding in women with OCD. Parenting dimensions are not related to hoarding in men. These findings provide further support for a hoarding subtype of OCD and for sex-specific differences in etiologic pathways for hoarding in OCD.

An investigation of doubt in obsessive-compulsive disorder.

BACKGROUND: Clinicians have long considered doubt to be a fundamental characteristic of obsessive-compulsive disorder (OCD). However, the clinical relevance of doubt in OCD has not been addressed. METHODS: Participants included 1182 adults with OCD who had participated in family and genetic studies of OCD. We used a clinical measure of the severity of doubt, categorized as none, mild, moderate, severe, or extreme. We evaluated the relationship between doubt and OCD clinical features, Axis I disorders, personality and personality disorder dimensions, impairment, and treatment response. RESULTS: The severity of doubt was inversely related to the age at onset of OCD symptoms. Doubt was strongly related to the number of checking symptoms and, to a lesser extent, to the numbers of contamination/cleaning and hoarding symptoms. Doubt also was related to the lifetime prevalence of recurrent major depression and generalized anxiety disorder; to the numbers of avoidant, dependent, and obsessive-compulsive personality disorder traits; and to neuroticism and introversion. Moreover, doubt was strongly associated with global impairment and poor response to cognitive behavioral treatment (CBT), even adjusting for OCD severity and other correlates of doubt. CONCLUSIONS: Doubt is associated with important clinical features of OCD, including impairment and cognitive-behavioral treatment response.

Stop Signal Reaction Time Deficits in a Lifetime Obsessive-Compulsive Disorder Sample.

OBJECTIVES: Several studies have found impaired response inhibition, measured by a stop-signal task (SST), in individuals who are currently symptomatic for obsessive-compulsive disorder (OCD). The aim of this study was to assess stop-signal reaction time (SSRT) performance in individuals with a lifetime diagnosis of OCD, in comparison to a healthy control group. This is the first study that has examined OCD in participants along a continuum of OCD severity, including approximately half of whom had sub-syndromal symptoms at the time of assessment. METHODS: OCD participants were recruited primarily from within the OCD clinic at a psychiatric hospital, as well as from the community. Healthy controls were recruited from the community. We used the stop signal task to examine the difference between 21 OCD participants (mean age, 42.95 years) and 40 healthy controls (mean age, 35.13 years). We also investigated the relationship between SST and measures of OCD, depression, and anxiety severity. RESULTS: OCD participants were significantly slower than healthy controls with regard to mean SSRT. Contrary to our prediction, there was no correlation between SSRT and current levels of OCD, anxiety, and depression severity. CONCLUSIONS: Results support prior studies showing impaired response inhibition in OCD, and extend the findings to a sample of patients with lifetime OCD who were not all currently above threshold for diagnosis. These findings indicate that response inhibition deficits may be a biomarker of OCD, regardless of current severity levels. (JINS, 2016, 22, 785-789).

OBSESSIVE-COMPULSIVE PERSONALITY DISORDER: EVIDENCE FOR TWO DIMENSIONS.

BACKGROUND: To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage. METHODS: Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors. Using MERLIN and MINX, we performed genome-wide quantitative trait locus (QTL) linkage analysis to test for allele sharing among individuals. RESULTS: Two factors were identified: Factor 1: order/control (perfectionism, excessive devotion to work, overconscientiousness, reluctance to delegate, and rigidity); and Factor 2: hoarding/indecision (inability to discard and indecisiveness). Factor 1 score was associated with poor insight, whereas Factor 2 score was associated with task incompletion. A significant sib-sib correlation was found for Factor 2 (rICC = .354, P < .0001) but not Factor 1 (rICC = .129, P = .084). The linkage findings were different for the two factors. When Factor 2 was analyzed as a quantitative trait, a strong signal was detected on chromosome 10 at marker d10s1221: KAC LOD = 2.83, P = .0002; and marker d10s1225: KAC LOD = 1.35, P = .006. CONCLUSIONS: The results indicate two factors of OCPD, order/control and hoarding/indecision. The hoarding/indecision factor is familial and shows modest linkage to a region on chromosome 10.

Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers.

OBJECTIVE: Current chronic pain treatments target nociception rather than affective "suffering" and its associated functional and psychiatric comorbidities. The left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can non-invasively modulate cortical activity. The present study tests whether anodal tDCS targeting the left DLPFC will increase tolerability of acute painful stimuli vs cathodal tDCS. METHODS: Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting the left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. RESULTS: Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (allP > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal vs cathodal tDCS (P = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (P = 0.042) on CP threshold, suggesting task sensitization. CONCLUSIONS: Although our results do not suggest that polarity of tDCS targeting the left DLPFC differentially modulates the tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting the left dorsal anterior cingulate cortex showed a trend toward higher mean CP tolerance with cathodal vs anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by the DVPRS. Sham-controlled clinical studies are needed.

Longitudinal course of body-focused repetitive behaviors in obsessive-compulsive disorder.

BACKGROUND: The course of body-focused repetitive behaviors (BFRBs) (eg, trichotillomania, skin picking, and nail biting) has received scant research attention. We sought to understand the longitudinal course of BFRBs over an 8-year period and whether the co-occurrence of a BFRB with obsessive-compulsive disorder (OCD) affects the course of OCD. METHODS: Three hundred ninety-five participants with OCD completed annual interviews using the Longitudinal Interval Follow-up Evaluation to estimate BFRB and OCD symptom severity during each week of follow-up. RESULTS: Of the 395 participants, 83 (21%) had a co-occurring BFRB. In almost one-half of the participants, BFRB onset occurred before OCD. Participants with OCD and BFRB spent the majority of the rating period experiencing full BFRB symptoms. Having a BFRB was associated with spending less time in remission from OCD. CONCLUSIONS: Although BFRBs have long been known to be common in individuals with OCD, these data demonstrate that most individuals who have a co-occurring BFRB with OCD do not experience BFRB remission and that having a BFRB predicts a worse course for OCD.

Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Distress Tolerance: A Preliminary Study.

OBJECTIVE: Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal ("inhibitory") stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli vs anodal stimulation. METHODS: Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. RESULTS: Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal vs anodal stimulation (P = 0.055) for participants self-completing the task. Pressure algometer (P = 0.81) and breath holding tolerance (P = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all P < 0.008). Pain intensity ratings increased acutely after cold pressor and pressure algometer tasks (both P < 0.01), but not after breath holding (P = 0.099). Cold pressor pain ratings tended to rise less after cathodal vs anodal tDCS (P = 0.072). CONCLUSIONS: Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation.

Who qualifies for deep brain stimulation for OCD? Data from a naturalistic clinical sample.

A few patients with obsessive-compulsive disorder (OCD) remain severely impaired despite exhausting best-practice treatments. For them, neurosurgery (stereotactic ablation or deep brain stimulation) might be considered. The authors investigated the proportion of treatment-seeking OCD patients, in a naturalistic clinical sample, who met contemporary neurosurgery selection criteria. Using comprehensive baseline data on diagnosis, severity, and treatment history for adult patients from the NIMH-supported Brown Longitudinal OCD Study, only 2 of 325 patients met screening criteria for neurosurgery. This finding prompts consideration of new models for clinical trials with limited samples as well as methods of refining entry criteria for such invasive treatments.

Excluding the typical patient: thirty years of pharmacotherapy efficacy trials for obsessive-compulsive disorder.

BACKGROUND: Over the past 30 years, clinical trials have resulted in several successful pharmacotherapies for obsessive-compulsive disorder (OCD), yet patients in clinical settings often report inadequate response. This study compares clinical characteristics of treatment-seeking OCD patients to the inclusion/exclusion criteria used in pharmacotherapy trials. METHODS: The sample consisted of 325 community members with a DSM-IV diagnosis of OCD who underwent systematic interviews with clinicians knowledgeable in the diagnosis and treatment of OCD. We compiled pharmacotherapy studies for OCD published between 1980 and 2010 using Medline, PubMed, and library resources, and estimated the proportion of patients in each decade satisfying the most common inclusion/exclusion criteria. RESULTS: We included 39 clinical trials and found 72% of the 325 patients would have been excluded from trials conducted between 1980 and 2010. Exclusion was projected as dramatically lower for trials conducted between 1980 and 1989 (19.7%) compared with 74.8% for trials conducted between 1990 and 1999 and 76.9% for trials between 2000 and 2010. CONCLUSIONS: The majority of treatment-seeking individuals with OCD would not qualify for OCD treatment studies due to comorbid psychiatric disorders, and failure to meet OCD severity threshold criteria. This illustrates the need to include a more community-representative sample of OCD patients in clinical trials examining pharmacotherapy efficacy.

OCD behavior therapy before and after gamma ventral capsulotomy: case report.

We report the case of a patient requiring gamma ventral capsulotomy (GVC), a neurosurgical intervention to address severe refractory obsessive-compulsive disorder (OCD). GVC involves stereotactic lesions in the ventral anterior limb of the internal capsule and adjacent ventral striatum. This study details the course of an extinction-based behavioral therapy, namely exposure and response prevention (ERP). The patient experienced significant changes in motivation and ability to tolerate ERP post-surgery. Furthermore, he was better able to absorb and remember exposure sessions. GVC surgery may affect the neural mechanisms involved in the extinction learning process, the same process implicated in ERP treatment.

Long-term course of pediatric obsessive-compulsive disorder: 3 years of prospective follow-up.

OBJECTIVE: This study assesses the long-term course of treatment-seeking youth with a primary diagnosis of DSM-IV OCD. METHOD: Sixty youth and their parents completed intake interviews and annual follow-up interviews for 3 years using the youth version of the Longitudinal Interval Follow-up Evaluation (Y-LIFE) and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Remission was defined as no longer meeting DSM-IV criteria for OCD for 8 weeks or more, and recurrence was defined as meeting full criteria for OCD for 4 consecutive weeks after having achieved symptom remission. Remission rates for youth were compared to rates of adults participating in the same study. RESULTS: The probability of achieving partial remission of OCD was 0.53 and the probability of achieving full remission was 0.27. Among the 24 youth participants who achieved remission, 79% stayed in remission throughout the study (mean of 88 weeks of follow-up) and 21% experienced a recurrence of symptoms. Better functioning at intake and a shorter latency to initial OCD treatment were associated with faster onset of remission (P<.001). CONCLUSIONS: Remission is more likely among youth versus adults with OCD. Treatment early in the course of illness and before substantial impact on functioning predicted a better course.

Clinical correlates and genetic linkage of social and communication difficulties in families with obsessive-compulsive disorder: Results from the OCD Collaborative Genetics Study.

Some individuals with obsessive-compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical examinations on, and collected DNA samples from, 706 individuals with OCD in 221 multiply affected OCD families. Using the Pragmatic Rating Scale (PRS), we compared the prevalence of pragmatic impairment in OCD-affected relatives of probands with and without pragmatic impairment. We also compared clinical features of OCD-affected individuals in families having at least one, versus no, individual with pragmatic impairment, and assessed for linkage to OCD in the two groups of families. The odds of pragmatic impairment were substantially greater in OCD-affected relatives of probands with pragmatic impairment. Individuals in high-PRS families had greater odds of separation anxiety disorder and social phobia, and a greater number of schizotypal personality traits. In high-PRS families, there was suggestive linkage to OCD on chromosome 12 at marker D12S1064 and on chromosome X at marker DXS7132 whereas, in low-PRS families, there was suggestive linkage to chromosome 3 at marker D3S2398. Pragmatic impairment aggregates in OCD families. Separation anxiety disorder, social phobia, and schizotypal personality traits are part of a clinical spectrum associated with pragmatic impairment in these families. Specific regions of chromosomes 12 and X are linked to OCD in high-PRS families. Thus, pragmatic impairment may distinguish a clinically and genetically homogeneous subtype of OCD.

"I Feel Like I Have Lost Part Of My Identity" - A Qualitative Study Exploring The Impact Of Chronic Ankle Instability.

Introduction: Lateral ankle sprain is the most common ankle injury and up to 40% of those who sustain a lateral ankle sprain will develop chronic ankle instability (CAI). The aim of this study was to explore the thoughts and expectations of CAI-patients concerning their condition and expectations of care in an orthopedic setting. . Study Design: Qualitative study. Methods: Nine semi-structured one-to-one interviews were conducted with CAI-patients who were referred to an orthopedic setting. Interviews were recorded, transcribed, and analyzed using systematic text condensation with an inductive goal free approach. . Results: Seven themes emerged. The themes were Injury history and symptoms (Lateral ankle sprain during sport, pain and instability), Information from health professional (conflicting information about management and prognosis), Management (mental and physical challenges), Expectation and hope (explanation of symptoms, prognosis and imaging to provide clarification of condition), Activity and participation (restriction in sport and daily life and feelings of uncertainty), Support (support from family/friends) and Identity (low ability to participate in sport and social life result in loss of identity). . Conclusion: The impact of CAI exceeds an experience of pain and instability. Patients experienced loss of identity, having to manage uncertainty regarding their diagnosis and prognosis and had hopes of being able to explain their condition. . Level of Evidence: Not applicable.

Course and clinical correlates of obsessive-compulsive disorder with or without comorbid personality disorder.

BACKGROUND: Personality disorders (PDs) are often comorbid with obsessive-compulsive disorder (OCD) which may influence symptom presentation and course. This investigation sought to examine the impact of comorbid PDs on clinical presentation and symptom chronicity in a large, prospective longitudinal OCD study. METHODS: Participants (n = 263) were treatment-seeking adults with a primary diagnosis of OCD separated into two groups: individuals with and without a co-occurring PD. We conducted two-tailed t-tests to compare symptom severity, functioning, and quality of life between the OCD + PD group (n = 117) and the OCD w/o PD group (n = 146). Chronicity analyses were conducted to compare the amount of time in-episode for OCD and major depressive disorder (MDD) between the two groups. RESULTS: The OCD + PD group reported greater OCD and depression severity, lower levels of psychosocial functioning and worse quality of life than the OCD w/o PD group. The OCD + PD group exhibited greater OCD and MDD symptom chronicity; over 5 years the OCD + PD group spent 16.2 % weeks longer at full criteria for OCD and three times as many weeks in episode for MDD than the OCD w/o PD group. LIMITATIONS: Focusing on PDs as a group limited our ability to make observations about specific PDs. Further, the participants in our sample were predominantly White and all were treatment seeking which limits the generalizability of our findings. CONCLUSIONS: Our results suggest that those with OCD and comorbid PDs present with greater overall impairment and may require additional considerations during treatment conceptualization and planning.

Examining relationships among NODDI indices of white matter structure in prefrontal cortical-thalamic-striatal circuitry and OCD symptomatology.

Obsessive-compulsive disorder is a psychiatric disorder characterized by intrusive thoughts and repetitive behaviors. There are two prominent features: Harm Avoidance (HA) and Incompleteness (INC). Previous resting-state studies reported abnormally elevated connectivity between prefrontal cortical (PFC) and subcortical regions (thalamus, striatum) in OCD participants. Yet, little is known about the white matter (WM) structural abnormalities in these connections. Using brain parcellation and segmentation, whole brain tractography, and Neurite Orientation Dispersion and Density Imaging (NODDI), we aimed to characterize WM structural abnormalities in OCD vs. healthy controls and determine the extent to which NODDI indices of these connections were associated with subthreshold-threshold HA, INC and overall OCD symptom severity across all participants. Four PFC regions were segmented: ventral medial (vmPFC), ventrolateral (vlPFC), dorsomedial (dmPFC), and dorsolateral (dlPFC). NODDI Neurite Density (NDI) and Orientation Dispersion (ODI) indices of WM structure were extracted from connections between these PFC regions and the thalamus (42 OCD, 44 healthy controls, mean age[SD] = 23.65[4.25]y, 63.9% female) and striatum (38 OCD, 41 healthy controls, mean age[SD] = 23.59[4.27]y, 64.5% female). Multivariate analyses of covariance revealed no between-group differences in these indices. Multivariate regression models revealed that greater NDI in vmPFC-thalamus, greater NDI and ODI in vmPFC-striatum, and greater NDI in dmPFC-thalamus connections were associated with greater INC severity (Q ≤ 0.032). These findings highlight the utility of NODDI in the examination of WM structure in OCD, provide valuable insights into specific WM alterations underlying dimensional INC, and can facilitate the development of customized treatments for OCD individuals with treatment-resistant symptoms.

Specific Patterns of Endogenous Functional Connectivity Are Associated With Harm Avoidance in Obsessive-Compulsive Disorder.

BACKGROUND: Individuals with obsessive-compulsive disorder (OCD) show persistent avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomical studies of persistent avoidance in rodents and nonhuman primates, our goal was to test whether connections within a hypothesized persistent avoidance-related network predicted OCD-related harm avoidance (HA), a trait measure of persistent avoidance. We hypothesized that 1) HA, not an OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2) HA-specific findings would be robust to comorbid symptoms; and 3) reliable findings would replicate in a holdout testing subsample. METHODS: Using resting-state functional connectivity magnetic resonance imaging, cross-validated elastic net for feature selection, and Poisson generalized linear models, we tested which connections significantly predicted HA in our training subsample (n = 73; 71.8% female; healthy control group n = 36, OCD group n = 37); robustness to comorbidities; and replicability in a testing subsample (n = 30; 56.7% female; healthy control group n = 15, OCD group n = 15). RESULTS: Stronger inverse connectivity between the right dorsal anterior cingulate cortex and right basolateral amygdala and stronger positive connectivity between the right ventral anterior insula and left ventral striatum were associated with greater HA across groups. Network connections did not discriminate OCD diagnostic status or predict HA-correlated traits, suggesting sensitivity to trait HA. The dorsal anterior cingulate cortex-basolateral amygdala relationship was robust to controlling for comorbidities and medication in individuals with OCD and was also predictive of HA in our testing subsample. CONCLUSIONS: Stronger inverse dorsal anterior cingulate cortex-basolateral amygdala connectivity was robustly and reliably associated with HA across groups and in OCD. Results support the relevance of a cross-species persistent avoidance-related network to OCD, with implications for precision-based approaches and treatment.