Closed-loop recruitment of striatal parvalbumin interneurons prevents the onset of compulsive behaviors

A prominent electrophysiological feature of compulsive behaviours is striatal hyperactivity; but its underlying dysfunctional cellular mechanisms still need to be characterized. Within the striatum, parvalbumin-positive interneurons (PVI) exert a powerful feedforward inhibition essential for the regulation of striatal activity. To investigate the potential implication of striatal PVI in aberrant repetitive behaviors, we used the Sapap3 mutant mice which exhibit compulsive-like behaviours characterized by excessive self-grooming. When striatal PVI in the centromedial striatum of Sapap3 mice were we optogenetically activated, we first showed that the number of compulsive-like events were greatly reduced. To investigate further the critical time-window when striatal PVI needed to be recruited for the behavioural regulation of compulsive-like grooming, we then designed a novel closed-loop stimulation pipeline. We identified a transient 1-4 Hz oscillations in the orbitofrontal cortex that temporally predicted grooming onsets. Exploiting this delta band signal as a biomarker, we were able to provide on-demand stimulation of striatal PVI shortly before predicted grooming events. This targeted closed-loop optogenetics approach greatly reduced grooming events and demonstrated that the recruitment of striatal PVI regulated the initiations of compulsive-like behaviours.

A Case of Obsessive-Compulsive Disorder Triggered by the Pandemic

Background: The pandemic caused by the sars-cov2 coronavirus can be considered the biggest international public health crisis. Outbreaks of emerging diseases can trigger fear reactions. Strict adherence to the strategies can cause harmful consequences, particularly for people with pathology on the spectrum of obsessive-compulsive disorder. Case presentation: We describe the clinical case of a woman, with a history of anxiety disorder, who develops obsessive-compulsive symptoms, she started cognitive behavioral therapy and pharmacological therapy, with appropriate follow-up. Conclusions: The intense focus on the risk of contamination and the adoption of new hygienic behaviors can be internalized as normative and become an enhancing trigger for obsessive thinking and compulsive behaviors. It is an important focus on prevention, early intervention and adequate follow-up, through measures to promote mental health.

Transdiagnostic Perspective of Impulsivity and Compulsivity in Obesity: From Cognitive Profile to Self-Reported Dimensions in Clinical Samples with and without Diabetes

Impulsive and compulsive behaviors have both been observed in individuals with obesity. The co-occurrence of obesity and type 2 diabetes (T2D) is more strongly associated with impulsivity, although there are no conclusive results yet. A multidimensional assessment of impulsivity and compulsivity was conducted in individuals with obesity in the absence or presence of T2D, compared with healthy, normal-weight individuals, with highly impulsive patients (gambling disorders), and with highly compulsive patients (anorexia nervosa). Decision making and novelty seeking were used to measure impulsivity, and cognitive flexibility and harm avoidance were used for compulsivity. For impulsivity, patients with obesity and T2D showed poorer decision-making ability compared with healthy individuals. For compulsivity, individuals with only obesity presented less cognitive flexibility and high harm avoidance; these dimensions were not associated with obesity with T2D. This study contributes to the knowledge of the mechanisms associated with diabetes and its association with impulsive–compulsive behaviors, confirming the hypothesis that patients with obesity and T2D would be characterized by higher levels of impulsivity.

Genetic Markers as Risk Factors for the Development of Impulsive-Compulsive Behaviors in Patients with Parkinson’s Disease Receiving Dopaminergic Therapy

Impulsive–compulsive and related behavioral disorders (ICD) are drug-induced non-motor symptoms of Parkinson’s disease (PD). Recently research has focused on evaluating whether ICD could be predicted and managed using a pharmacogenetic approach based on dopaminergic therapies, which are the main risk factors. The aim of our study was to evaluate the role of candidate genes such as DBH, DRD2, MAOA, BDNF, COMT, SLC6A4, SLC6A3, ACE, DRD1 gene polymorphisms in the pathogenesis of ICD in PD. We compared patients with PD and ICD (n = 49), patients with PD without ICD (n = 36) and a healthy control group (n = 365). ICD was diagnosed using the QUIP questionnaires and specific diagnostic criteria for subtypes of ICD. Genotyping was conducted using a number of PCR techniques and SNaPshot. Statistical analysis was performed using WinPepi and APSampler v3.6 software. PCA testing was conducted using RStudio software v1.4.1106-5. The following substitutions showed statistically significant correlations with PD and ICD: DBH (rs2097629, rs1611115), DRD2 (rs6275, rs12364283, rs1076560), ACE (rs4646994), DRD1 (rs686), BDNF (rs6265), these associations are novel in Russian PD patients. Our findings suggest that polymorphisms in DBH, BDNF, DRD2, ACE genes in Russian subjects are associated with an increased risk of ICD development.

The prevalence of impulsive compulsive behaviors in patients treated with apomorphine infusion: a retrospective analysis

ABSTRACT Background: Impulsive compulsive behaviors (ICBs) can affect a significant number of Parkinson’s disease (PD) patients. Objective: We have studied brain samples from a brain bank of PD patients who received apomorphine via continuous infusion in life to assess the prevalence and outcome of ICBs. Methods: A search on the Queen Square Brain Bank (QSBB) database for cases donated from 2005 to 2016 with a pathological diagnosis of idiopathic PD was conducted. Notes of all donors who used apomorphine via continuous infusion for at least three months were reviewed. Clinical and demographic data were collected, as well as detailed information on treatment, prevalence and outcomes of ICBs. Results: 193 PD cases, 124 males and 69 females, with an average age at disease onset of 60.2 years and average disease duration of 17.2 years were reviewed. Dementia occurred in nearly half of the sample, depression in one quarter, and dyskinesias in a little over 40%. The prevalence of ICBs was 14.5%. Twenty-four individuals used apomorphine infusion for more than three months. Patients on apomorphine had younger age at disease onset, longer disease duration, and higher prevalence of dyskinesias. The prevalence of de novo ICB cases among patients on apomorphine was 8.3%. Apomorphine infusion was used for an average of 63.1 months on an average maximum dose of 79.5 mg per day. Ten patients remained on apomorphine until death. Conclusions: Apomorphine can be used as an alternative treatment for patients with previous ICBs as it has low risk of triggering recurrence of ICBs.

Stress deceleration theory: chronic adolescent stress exposure results in decelerated neurobehavioral maturation

Normative development in adolescence indicates that the prefrontal cortex is still under development thereby unable to exert efficient top-down inhibitory control on subcortical regions such as the basolateral amygdala and the nucleus accumbens. This imbalance in the developmental trajectory between cortical and subcortical regions is implicated in expression of the prototypical impulsive, compulsive, reward seeking and risk-taking adolescent behavior. Here we demonstrate that a chronic mild unpredictable stress procedure during adolescence in male Wistar rats arrests the normal behavioral maturation such that they continue to express adolescent-like impulsive, hyperactive, and compulsive behaviors into late adulthood. This arrest in behavioral maturation is associated with the hypoexcitability of prelimbic cortex (PLC) pyramidal neurons and reduced PLC-mediated synaptic glutamatergic control of BLA and nucleus accumbens core (NAcC) neurons that lasts late into adulthood. At the same time stress exposure in adolescence results in the hyperexcitability of the BLA pyramidal neurons sending stronger glutamatergic projections to the NAcC. Chemogenetic reversal of the PLC hypoexcitability decreased compulsivity and improved the expression of goal-directed behavior in rats exposed to stress during adolescence, suggesting a causal role for PLC hypoexcitability in this stress-induced arrested behavioral development.

Irritability, Defiant and Obsessive-Compulsive Problems Development from Childhood to Adolescence

Little is known about the coexistence of oppositionality and obsessive-compulsive problems (OCP) in community children and how it affects their development until adolescence to prevent possible dysfunctions. The co-development of oppositional defiant dimensions and OCP is studied in 563 children (49.7% female) from ages 6 to 13 years, assessed yearly with measures answered by parents and teachers. A 4-class model based on Latent Class Growth Analysis for three parallel processes (irritability, defiant, and OCP) was selected, which showed adequate fitting indexes. Class 1 (n = 349, 62.0%) children scored low on all the measures. Class 2 (n = 53, 9.4%) contained children with high OCP and low irritability and defiant. Class 3 (n = 108, 19.2%) clustered children with high irritability and defiant and low OCP. Class 4 (n = 53, 9.4%) clustered comorbid irritability, defiant, and OCP characteristics. The classes showed different clinical characteristics through development. The developmental co-occurrence of irritability and defiant plus obsessive-compulsive behaviors is frequent and adds severity through development regarding comorbidity, peer problems, executive functioning difficulties, and daily functioning. The identification of different classes when combining oppositional problems and OCP may be informative to prevent developmental dysfunctions and to promote good adjustment through development.

Validation of the Arabic version of the Dusseldorf Orthorexia Scale (DOS) among Lebanese adolescents

Background Orthorexia Nervosa (ON) is defined as a pathological preoccupation characterized by obsessive beliefs and compulsive behaviors regarding 'pure' eating behaviors. Many scales have been established and display good results regarding reliability and validity measures, including but not limited to ORTO-R (revised version of ORTO-15), Eating Habits Questionnaire, Teruel Orthorexia Scale (TOS) and the Düsseldorf Orthorexia Scale (DOS). Among these, the DOS seems to be a promising measure for multiple reasons. The current paper aims to validate the DOS, a measure of ON, in a non-Western population of Lebanese adolescents. Methods This was a cross-sectional designed study, conducted between May and June 2020, which enrolled 555 adolescents (15–18 years old; 75.7% females). Due the coronavirus pandemic outbreak, the data were gathered through snowball sampling using an online questionnaire. The DOS, TOS and ORTO-R scales were used in this study to screen for orthorexic tendencies and behaviors. Results We tested four competing structural models of the DOS assessing its factorial validity. The results of the current investigation revealed that the one-factorial model is the best one to represent the structure of the questionnaire. We provided evidence for validity for the DOS through demonstrating that it correlates significantly with other measures of orthorexic behaviours (Teruel Orthorexia Scale and ORTO-R). Finally, we have gathered evidence that the orthorexic behaviours as measured by DOS are not associated with age (r = −.02; p = .589), household crowding index (r = .02; p = .578), and Body Mass Index (r = .04; p = .297). Yet, females as compared to males achieved higher scores (M = 20.07, SD = 6.38 vs M = 18.29, SD = 6.37; p = .005; d = .28). Conclusion The Arabic version of the DOS seems to be a structurally valid and internally consistent questionnaire measuring orthorexic eating behavior in a sample of Lebanese adolescents. This tool may be useful for psychologists, psychiatrists, dietitians and other clinicians in the assessment and the treatment of the multidimensional nature of ON.

9 The Effects of Feeding Cannabidiol Oil on Behavior of Stalled Horses

Using cannabidiol (CBD) in animals has increased since the 2018 Agricultural Improvement Act was passed. Previous work in laboratory animals suggests supplementation with CBD reduced anxiety, compulsive behaviors, and brain activity of limbic and paralimbic areas. Horses exhibit anxiety due to training or housing situations, which is sometimes expressed via stereotypic behaviors including cribbing, aggression, etc. These behaviors can indicate underlying stressors and sometimes causes impairment; therefore, supplementing CBD may reduce undesirable behaviors in horses, consequently improving the health and overall welfare. The study objective was to determine if a single oral dose of CBD would result in adverse effects in horses. Four mature mares and four mature geldings were used in a randomized-control treatment design. Horses typically housed in paddocks, but not novel to stalling were housed in 11’ X 14’ stalls with cameras to record behavior, feed, and water intake. Horses were acclimated to feeding methods and stall environment for one week. Behavior was recorded for 24hr after a dosage of olive oil was administered as a control (CON). Horses were returned to their paddock for one week, then randomly assigned to either a LOW (0.3mg/kg BW; n = 4) or HIGH (0.6 mg/kg BW; n = 4) treatment of CBD oil. After oral dosing, horses were stalled for observation. Stereotypic behaviors such as pawing, cribbing, and aggression were quantified using the Observer XTTM program. Observations were analyzed in R Studio© for analysis of variance (ANOVA). The occurrence of stereotypic behaviors was lower (P = 0.03) in horses given oral CBD. Actions occurred more frequently during feeding sessions, behaviors including aggression and pawing occurred less when horses were given the High dose compared to Control (113 to 26 and 69 to 27) respectively. Based on results, oral administration of the particular cannabidiol product used in this study may mediate negative behaviors in stalled horses.