Transfer of information across repeated decisions in general and in obsessive-compulsive disorder.

Real-life decisions are often repeated. Whether considering taking a job in a new city, or doing something mundane like checking if the stove is off, decisions are frequently revisited even if no new information is available. This mode of behavior takes a particularly pathological form in obsessive-compulsive disorder (OCD), which is marked by individuals' redeliberating previously resolved decisions. Surprisingly, little is known about how information is transferred across decision episodes in such circumstances, and whether and how such transfer varies in OCD. In two experiments, data from a repeated decision-making task and computational modeling revealed that both implicit and explicit memories of previous decisions affected subsequent decisions by biasing the rate of evidence integration. Further, we replicated previous work demonstrating impairments in baseline decision-making as a function of self-reported OCD symptoms, and found that information transfer effects specifically due to implicit memory were reduced, offering computational insight into checking behavior.

Noncanonical cytoplasmic poly(A) polymerases regulate RNA levels, alternative RNA processing, and synaptic plasticity but not hippocampal-dependent behaviours.

Noncanonical poly(A) polymerases are frequently tethered to mRNA 3' untranslated regions and regulate poly(A) tail length and resulting translation. In the brain, one such poly(A) polymerase is Gld2, which is anchored to mRNA by the RNA-binding protein CPEB1 to control local translation at postsynaptic regions. Depletion of CPEB1 or Gld2 from the mouse hippocampus results in a deficit in long-term potentiation (LTP), but only depletion of CPEB1 alters animal behaviour. To test whether a related enzyme, Gld4, compensates for the lack of Gld2, we separately or simultaneously depleted both proteins from hippocampal area CA1 and again found little change in animal behaviour, but observed a deficit in LTP as well as an increase in long-term depression (LTD), two forms of protein synthesis-dependent synaptic plasticity. RNA-seq data from Gld2, Gld4, and Gld2/Gld4-depleted hippocampus show widespread changes in steady state RNA levels, alternative splicing, and alternative poly(A) site selection. Many of the RNAs subject to these alterations encode proteins that mediate synaptic function, suggesting a molecular foundation for impaired synaptic plasticity.

Chest Wall Mobility: Identification of Underlying Predictors.

OBJECTIVE: The purpose of this study was to identify factors contributing to normal mobility or hypermobility of the chest wall. METHODS: Seventy-eight young adults were divided into 2 groups: patients with normal mobility (group 1, n = 40) and hypermobility of the chest wall (group 2, n = 38). The mean mobility of the chest wall in groups 1 and 2 was 9.9 and 6.1 cm, respectively. The mean age of groups 1 and 2 was 22.2 and 21.5 years, respectively. The Brief Symptom Inventory, State-Trait Anxiety Inventory, Beck Depression Inventory, and the Perceived Stress Scale were used to evaluate the psychometric properties. Quality of life was assessed using 12-Item Short Form Health Survey. Smoking status was determined via self-report of current smoking status. Chest wall mobility was measured using thoracic and axillary cirtometry. Pulmonary functions were evaluated using a Spirobank II device. Subsequently, forced vital capacity (FVC), forced expiratory volume in 1 second, peak expiratory flow, and forced expiratory flow 25% to 75% were verified. Carefusion Micro RPM and the 6-minute walk test were used to evaluate maximal respiratory pressures and functional capacity, respectively. RESULTS: With backward linear regression models, FVC and obsessive-compulsive traits were significant predictors of chest wall mobility (R²â€¯= 0.27; P < .001 and P = .01, respectively). In logistic regression models, FVC, maximum inspiratory pressure, and obsessive-compulsive traits were significant predictors of normal mobility/hypermobility of the chest wall (R²â€¯= 0.42; P < .001, P = .01, and P = .03, respectively). CONCLUSION: Forced vital capacity, maximum inspiratory pressure, and obsessive-compulsive traits are significant predictors of chest wall mobility and normal mobility or hypermobility of the chest wall.

Is sustained attention deficit related to subclinical obsessive thoughts in children and adolescents with ADHD?

Background: Thought content and its impact on sustained attention in individuals with attention deficit hyperactivity disorder (ADHD) are topics of growing interest in literature.Objective: We hypothesised that subclinical obsessive thoughts may be correlated with attention lapses in individuals with ADHD.Method: Thirty children diagnosed with ADHD participated in the study and their level of subclinical obsessive thoughts, attention, and executive function were measured using Children Yale-Brown Obsessive Scale and Conners' Continuous Performance Test II.Results: No significant correlation between sustained attention impairment and the level of obsessive thoughts in patients with ADHD was found. Nevertheless, patients with ADHD with subclinical obsessive thoughts showed more commission errors than those without (W = 51.5; p = 0.02).Conclusion: The nature of thought content in individuals with ADHD should be linked to executive dysfunction rather than attentional impairment. This could be of importance in the therapeutic strategy choice, addressing the importance of executive function remediation in the specific context of subclinical obsessive thoughts.Key points Patients with ADHD, without OCD or ASD comorbidity, still present subclinical obsessive thoughts (36% of our sample). • Subclinical obsessive thoughts could be a part of thought content in patients with ADHD. • Subclinical obsessive thoughts as measured by the CPT-II are not correlated with attention function in patients with ADHD. • ADHD patients with subclinical obsessive symptoms present more impairment in response inhibition than the ones without. • Results on subclinical obsessive thoughts are similar to those on another type of thought content called 'mind wandering'. • A clinical improvement strategy for patients with ADHD could be using executive function remediation rather than classical attention function remediation, according to both to our and previous results.

OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency.

Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling. Excessive self-grooming, reflecting OCD-like behavior in rodents, resulted in facial skin lesions in SPRED2 knockout (KO) mice. This was alleviated by treatment with the selective serotonin reuptake inhibitor fluoxetine. In addition to the previously suggested involvement of cortico-striatal circuits, electrophysiological measurements revealed altered transmission at thalamo-amygdala synapses and morphological differences in lateral amygdala neurons of SPRED2 KO mice. Changes in synaptic function were accompanied by dysregulated expression of various pre- and postsynaptic proteins in the amygdala. This was a result of altered gene transcription and triggered upstream by upregulated tropomyosin receptor kinase B (TrkB)/ERK-MAPK signaling in the amygdala of SPRED2 KO mice. Pathway overactivation was mediated by increased activity of TrkB, Ras, and ERK as a specific result of SPRED2 deficiency and not elicited by elevated brain-derived neurotrophic factor levels. Using the MEK inhibitor selumetinib, we suppressed TrkB/ERK-MAPK pathway activity in vivo and reduced OCD-like grooming in SPRED2 KO mice. Altogether, this study identifies SPRED2 as a promising new regulator, TrkB/ERK-MAPK signaling as a novel mediating mechanism, and thalamo-amygdala synapses as critical circuitry involved in the pathogenesis of OCD.

Relationship between impulsivity and obsession types in obsessive-compulsive disorder.

OBJECTIVE: Impulsivity is an important aspect of obsessive-compulsive disorder (OCD) which is classified under a new heading in DSM-5 with other impulsivity related disorders like trichotillomania. Due to its heterogeneous nature, different obsessions may be linked to varying impulsivity profiles. Aim of this study was to investigate the impulsivity traits and their relationship with obsession types by comparing OCD subjects who display sexual, religious and aggressive obsessions or other obsessions to healthy controls. METHODS: Outpatients with OCD (n = 146) and healthy controls (n = 80) were evaluated with Sociodemographic Data Form, SCID-I, SCID non-patient version, Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Barratt Impulsiveness Scale (BIS-11). RESULTS: BIS-11 attention scores of the OCD group were significantly higher than healthy subjects. In patients with sexual, aggressive, religious obsessions, BIS-11 attention scores were significantly higher than those who have other obsession types and that of controls. CONCLUSIONS: Higher levels of attentional impulsivity, particularly in patients suffering from sexual, aggressive or religious obsessions suggest a common diathesis for a dysfunction in neural correlates corresponding to these symptoms. The results of our study may promote further studies conducted with more advanced and objective neuropsychometric tests evaluating features of the clinical course, neurobiology and the response to OCD treatment.

A maternally inherited 16p13.11-p12.3 duplication concomitant with a de novo SOX5 deletion in a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features.

We detail here the clinical description and the family genetic study of a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features and a combination of two rare genetic variants: a maternally inherited 16p13.11-p12.3 duplication and a de novo 12p12.1 deletion affecting SOX5. The 16p13.11 microduplication has been implicated in several neurodevelopmental and behavioral disorders and is characterized by variable expressivity and incomplete penetrance. The causes of this variation in phenotypic expression are not fully clear, representing a challenge in genetic diagnosis and counseling. However, several authors have proposed the two-hit model as one of the underlying mechanisms for this phenotypic heterogeneity. Our data could also support this two-hit model in which the 16p13.11-p12.3 duplication might contribute to the phenotype, not only as a single event but also in association with the SOX5 deletion. The SOX5 gene plays important roles in various developmental processes and has been associated with several neurodevelopmental disorders, mainly intellectual disability, developmental delay and language and/or speech delay as well as with behavior problems and dysmorphic features. However, many of the physical features and behavioral manifestations as well as language deficiencies present in our patient are consistent with those previously reported for SOX5 deletions. Patients carrying multiple genomic variants, as the one presented here, illustrate the difficulty in analyzing genotypes when the contribution of each variant results in overlapping phenotypes and/or, alternatively, in the modification of the clinical manifestations defined by the coexisting variant.

Increased orbitofrontal cortex activation associated with "pro-obsessive" antipsychotic treatment in patients with schizophrenia.

BACKGROUND: Patients with schizophrenia have an approximately 10-fold higher risk for obsessive-compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. METHODS: To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. RESULTS: We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. LIMITATIONS: The main limitation of this study is its cross-sectional design. CONCLUSION: To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations.

Perceptual properties of obsessive thoughts are associated with low insight in obsessive-compulsive disorder.

Obsessions are traditionally defined as bothersome and repetitive thoughts that the patient is unable to resist. Preliminary evidence suggests that in a subgroup of patients with obsessive-compulsive disorder (OCD), obsessions are experienced as partially perceptual. The present study explored the frequency of perceptually laden obsessions and their relationship with illness insight and depression. Twenty-six patients with OCD were administered the newly developed Sensory Properties of Obsessions Questionnaire. Participants were asked to endorse on a 5-point Likert scale whether their obsessions were associated with perceptual features. Participants showed moderate symptom severity. A total of 73% affirmed that their obsessions contained perceptual features. The predominant perceptual channels were visual, tactile, and somatic (i.e., bodily sensations). The extent of perceptual aspects associated with obsessions was strongly correlated with lack of insight (Yale-Brown Obsessive-Compulsive Scale item 11) but not depression severity. The present study suggests that obsessive thoughts are frequently accompanied by perceptual sensations, which concurs with models assuming a continuum between hallucinations and intrusions. Apparently, the more "real" or authentic the obsessive thought is experienced, the less the afflicted person is able to dismiss its content as fully irrational or absurd.

Worrying and rumination are both associated with reduced cognitive control.

Persistent negative thought is a hallmark feature of both major depressive disorder and generalized anxiety disorder. Despite its clinical significance, little is known about the underlying mechanisms of persistent negative thought. Recent studies suggest that reduced cognitive control might be an explanatory factor. We investigated the association between persistent negative thought and switching between internal representations in working memory, using the internal shift task (IST). The IST was administered to a group of undergraduates, classified as high-ruminators versus low-ruminators, or high-worriers versus low-worriers. Results showed that high-ruminators and high-worriers have more difficulties to switch between internal representations in working memory as opposed to low-ruminators and low-worriers. Importantly, results were only significant when the negative stimuli used in the IST reflected personally relevant worry themes for the participants. The results of this study indicate that rumination and worrying are both associated with reduced cognitive control for verbal information that is personally relevant.

Emotional cascades and self-injury: investigating instability of rumination and negative emotion.

OBJECTIVE: Nonsuicidal self-injury (NSSI) is a public health concern and risk factor for suicide. The Emotional Cascade Model (ECM) proposes that NSSI partially functions as a distraction from cascades of negative affect and rumination. The purpose of this study was to examine the roles of trait rumination, and momentary instability of rumination and negative emotion, in NSSI. METHOD: Experience sampling methods were used to monitor thoughts, emotions, and behaviors in 47 individuals reporting dysregulated behaviors including NSSI. Instability indices were generated for rumination and negative emotion using the momentary assessments. RESULTS: Twenty-five episodes of NSSI were reported during monitoring. Trait rumination prospectively predicted NSSI episodes, and the instability indices interacted to predict NSSI. CONCLUSIONS: Consistent with the ECM, the interaction between rumination instability and negative affect instability during monitoring significantly predicted NSSI, with the strongest effects occurring for sadness and rumination about past. These findings may enhance conceptualization and treatment of patients with NSSI.

Clinical and neurocognitive profiles of subjects at high risk for psychosis with and without obsessive-compulsive symptoms.

OBJECTIVE: Obsessive-compulsive symptoms (OCS), which are common in psychotic-spectrum illnesses, are of clinical interest because of their association with poor prognosis or cognitive dysfunction. However, few studies on the clinical and neurocognitive implications of OCS in individuals at ultra-high risk for psychosis (UHR) have been conducted. METHOD: Sixty-five UHR subjects [24 with OCS (UHR+OCS), 41 without OCS (UHR-OCS)], and 40 healthy controls were assessed using clinical scales and neurocognitive tests. RESULTS: Those with UHR+OCS showed more severe clinical symptoms and poorer global functioning as compared to both healthy controls and the UHR-OCS group, according to the results of the Global Assessment of Functioning, the Comprehensive Assessment of At-Risk Mental States, and the Positive and Negative Syndrome Scale (total, negative, and general scores). In the neurocognitive domain, those in the UHR-OCS group showed notably greater latency in the Stroop task and more confabulation errors in immediate recall in the Rey-Osterrieth Complex Figure Test compared with those in UHR+OCS group, whose performance levels were similar to those of the healthy control group. CONCLUSIONS: The OCS manifested in UHR individuals was associated with a more severe clinical symptomatic presentation, including lower global functioning and more psychotic symptoms. On the other hand, those with UHR-OCS performed more poorly on some cognitive tests. The features that distinguish the groups can be used for developing prognoses and intervention strategies for the heterogeneous UHR group.

Exercise addiction: symptoms, diagnosis, epidemiology, and etiology.

Regular physical activity plays a crucial role in health maintenance and disease prevention. However, excessive exercise has the potential to have adverse effects on both physical and mental health. The scholastic and empirical discussion of excessive physical activity focuses on obsessive and compulsive exercising, and uses several labels. However, in this review, we argue that the most appropriate term for this phenomenon is exercise addiction, emphasizing that excessive physical exercise fits the typical and most common characteristics of behavioral addictions. The aim of this review is to synthesize the current knowledge on symptomology, diagnosis, epidemiology, and etiology of exercise addiction.

Towards mouse models of perseveration: a heritable component in extinction of operant behavior in fourteen standard and recombinant inbred mouse lines.

Extinction of instrumental responses is an essential skill for adaptive behavior such as foraging. So far, only few studies have focused on extinction following appetitive conditioning in mice. We studied extinction of appetitive operant lever-press behavior in six standard inbred mouse strains (A/J, C3H/HeJ, C57BL/6J, DBA/2J, BALB/cByJ and NOD/Ltj) and eight recombinant inbred mouse lines. From the response rates at the end of operant and extinction training we computed an extinction index, with higher values indicating better capability to omit behavioral responding in absence of reward. This index varied highly across the mouse lines tested, and the variability was partially due to a significant heritable component of 12.6%. To further characterize the relationship between operant learning and extinction, we calculated the slope of the time course of extinction across sessions. While many strains showed a considerable capacity to omit responding when lever pressing was no longer rewarded, we found a few lines showing an abnormally high perseveration in lever press behavior, showing no decay in response scores over extinction sessions. No correlation was found between operant and extinction response scores, suggesting that appetitive operant learning and extinction learning are dissociable, a finding in line with previous studies indicating that these forms of learning are dependent on different brain areas. These data shed light on the heritable basis of extinction learning and may help develop animal models of addictive habits and other perseverative disorders, such as compulsive food seeking and eating.

Neurobehavioral phenotype in Prader-Willi syndrome.

The focus of this article is on the lifetime development of people with Prader-Willi syndrome (PWS) and specifically on the neurobehavioral phenotype. We consider studies of this aspect of the phenotype (the "behavioral phenotype" of the syndrome) that have confirmed that there are specific behaviors and psychiatric disorders, the propensities to which are increased in those with PWS, and cannot be accounted for by other variables such as IQ or adaptive behavior. Beginning with a description of what is observed in people with PWS, we review the evolving PWS phenotype and consider how some aspects of the phenotype might be best explained, and how this complex phenotype may relate to the equally complex genotype. We then consider in more detail some of the neurobehavioral aspects of the phenotype listed above that raise the greatest management problems for parents and carers.

Obsessive-compulsive behavior as a symptom of dementia in progressive supranuclear palsy.

AIMS: To describe obsessive-compulsive symptoms (OCS) as under-recognized behavioral and psychological symptoms of dementia of progressive supranuclear palsy (PSP) and to discuss possible mechanisms based on MRI and SPECT findings. METHODS: We studied 74 PSP patients. OCS are defined as persistent and unreasonable, but non-delusional/hallucinatory, ideas and behaviors. Demography, cognition, the widths of middle cerebellar peduncles (MCP) and the inter-caudate distances (ICD), both corrected by the intracranial size (MCP and ICD ratios), and changes on voxel-based SPECT were compared between the subgroups with and without OCS. Finally, the predicative power of various factors to OCS was investigated. RESULTS: We observed OCS in 18 patients (24%). They were obsessed with daily trifles and physical symptoms among other things. OCS was not associated with demography or cognitive levels. OCS-positive patients had significantly smaller MCP and ICD ratios and showed marked uptake decreases in the orbitofrontal cortex, caudate and thalamus. Relative uptake increases in the cerebellum, specifically the tonsils, were milder in OCS-positive than -negative patients. A smaller right MCP, a smaller ICD ratio and lower uptake increases in the right cerebellar were the significant predictors of OCS. CONCLUSIONS: OCS are frequent but under-recognized behavioral and psychological symptoms of dementia in PSP. Dysfunction of the fronto-caudate-thalamus-cerebellum circuit may be involved.

Anger rumination, social support, and cardiac symptoms in patients undergoing angiography.

OBJECTIVES: Socially isolated individuals report more cardiac symptoms, suffer increased cardiovascular morbidity and mortality, and experience higher levels of stress and anxiety than those with more effective support resources. However, the complex interactions of psychosocial factors implicated in the disease process remain to be fully elucidated. We sought to explore these relationships, with the addition of a novel psychosocial variable, anger rumination, which could be associated with increased cardiovascular risk. DESIGN: We examined the association of psychological stress, social support, and anger rumination, with surgical anxiety, self-reported cardiac symptoms, and angiographically documented coronary artery disease, using a correlational ex post facto design. METHODS: One hundred and one patients scheduled for elective coronary angiography completed questionnaires during the week prior to angiography. Disease severity was objectively assessed using the Gensini scoring system. RESULTS: Self-reported cardiac symptom severity was significantly correlated with higher perceived stress, less social support, and higher anger rumination, but none of the psychosocial variables predicted Gensini score. Social support partially mediated the relationship between anger rumination and surgical anxiety. Perceived stress mediated the relationship between anger rumination and cardiac symptoms. CONCLUSIONS: For patients awaiting angiography, stress, and lack of social support are important predictors of self-reported cardiac symptoms, irrespective of actual disease severity. Intervention could focus on reducing perceived stress by encouraging reappraisal and a support seeking, rather than a ruminative, anger coping style.

Contribution of left frontal-motor alpha phase synchronization to semantic inhibition in obsessive-compulsive tendencies.

Patients with obsessive-compulsive disorder attempt to suppress obsessions and/or compulsions. Although previous psychological research suggests reduced semantic inhibition in such patients, no research has explored the underlying neural mechanisms of semantic control in patients with obsessive-compulsive disorder. In addition to semantic representation, semantic control also generates task-relevant behaviors. Previous research has implicated the left frontal and posterior temporal areas in semantic control; however, no research approaches the dynamic relationships among task-relevant brain areas. To address this, we investigated the phase synchronizations among these areas using time-frequency analysis of data from an electroencephalograph, recorded during a semantic classification task. Participants were healthy patients whose obsessive-compulsive tendencies were assessed using a questionnaire. In this task, when presented with a red colored word, participants were required to classify it into categories as either plants or animals with a keypress (i.e. the classification condition). When presented with a green colored word, participants were required to read it without classification (i.e. the inhibition condition). The behavioral results showed that the semantic negative priming (i.e. the increase in reaction time to the word included in the previously inhibited category) was negatively correlated with obsessive-compulsive tendencies. Electroencephalograph results showed that the left frontal-motor alpha phase synchronization under the classification condition was significantly higher than under the inhibition condition. This phase synchronization under the inhibition condition was positively correlated with obsessive-compulsive tendencies. These results suggest that a dynamic link between the left frontal and motor areas may reflect reduced semantic inhibition in individuals with stronger obsessive-compulsive tendencies.

Obsessive-Compulsive Symptoms are Less Common in Huntington's Disease than Reported Earlier.

BACKGROUND: Previous research using the Symptom-Checklist-90-Revised (SCL-90-R) has shown that compulsive symptoms in Huntington's disease (HD) occur in 10% to 52% of all cases. The "Hamburger-Zwangsinventar" (HZI), a self-rating questionnaire comprising 188 items, taps into the domain of compulsiveness in greater detail, but has not been used in HD so far. In addition, little is known about the association of obsessive-compulsive symptoms with pre-clinical stages of HD. OBJECTIVE: Comparison of OC symptoms measured by the SCL-90-R and the HZI in pre-HD and HD. METHODS: 29 premanifest mutation carriers (pre-HD) and 40 manifest HD patients completed both questionnaires. Clinical characteristics of HD were rated by using the UHDRS. RESULTS: Compared to data from general population prevalence of OC symptoms were not higher as expected in preHD and only slightly elevated in manifest HD if using HZI. Both instruments detected more OC symptoms in HD patients compared to pre-HD. The SCL-90-R more often detects compulsivity than the HZI. Results of both questionnaires showed correlations to cognition, depression, and disease duration. Compared to findings from OCD patients, there was a subordinate role in the HZI subscale for "washing and cleaning" in HD. CONCLUSIONS: OC symptoms in pre-HD occur not more often than in general population. The HZI appears to be useful for examining OC symptoms in detail in pre-HD and HD. HZI-subscale ratings for washing and cleaning compulsions were less pronounced in HD compared to OCD patients, possibly due to loss of disgust. The SCL-90-R might overestimate OC symptoms in both groups.