A systematic review of focused ultrasound for psychiatric disorders: current applications, opportunities, and challenges.

OBJECTIVE: Advancements in MRI-guided focused ultrasound (MRgFUS) technology have led to the successful treatment of select movement disorders. Based on the comparative success between ablation and deep brain stimulation, interest arises in focused ultrasound (FUS) as a promising treatment modality for psychiatric illnesses. In this systematic review, the authors examined current applications of FUS for psychiatric conditions and explored its potential opportunities and challenges. METHODS: The authors performed a comprehensive review using the PRISMA guidelines of studies investigating psychiatric applications for FUS. Articles indexed on PubMed between 2014 to 2024 were included. The authors synthesized the psychiatric conditions treated, neural targets, outcomes, study design, and sonication parameters, and they reviewed important considerations for the treatment of psychiatric disorders with FUS. They also discussed active clinical trials in this research domain. RESULTS: Of 250 articles, 10 met the inclusion criteria. Eight articles investigated the clinical, safety, and imaging correlates of MRgFUS in obsessive-compulsive disorder (OCD), whereas 3 examined treatment-resistant depression. Bilateral anterior capsulotomy resulted in a full responder rate of 67% (≥ 35% reduction in the Yale-Brown Obsessive-Compulsive Scale score) and 33% (≥ 50% reduction in the score on the Hamilton Rating Scale for Depression) in OCD and treatment-resistant depression, respectively. Sonications ranged from 8 to 36 with targeted lesional temperatures of 51°C-56°C. Lesions in the anterodorsal aspect of the anterior limb of the internal capsule (ALIC) and increased functional connectivity to the left dorsolateral prefrontal cortex and dorsal anterior cingulate cortex significantly predicted reduction in symptoms among patients with OCD, with decreases in beta-band activity in the frontocentral and temporal regions associated with reductions in depression and anxiety. Treatment of the nucleus accumbens with low-intensity FUS (LIFU) in patients with opioid-use disorders resulted in significant reductions in cue-reactive cravings, lasting up to 90 days. No serious adverse events were reported, including cognitive decline. Side effects were generally mild and transient, consisting of headaches, pin-site swelling, and nausea. Fourteen active clinical trials were identified, primarily targeting depression with LIFU. CONCLUSIONS: Currently, FUS for psychiatric conditions is centered on OCD, with early pilot studies demonstrating promising safety and efficacy. Further research expanding on defining optimal patient selection, study design, intensity, and sonication parameters is warranted, particularly as FUS expands to other psychiatric illnesses and incorporates LIFU paradigms. Ethical considerations such as patient consent and equitable access also remain paramount.

Quantification of glutathione and its associated spontaneous neuronal activity in major depressive disorder and obsessive-compulsive disorder.

BACKGROUND: Glutathione (GSH) is a crucial antioxidant in the human brain. Although proton magnetic resonance spectroscopy (MRS) using the MEscher-GArwood Point RESolved Spectroscopy (MEGA-PRESS) sequence is highly recommended, limited literature has measured cortical GSH using this method in major psychiatric disorders. METHODS: By combining MRS using the MEGA-PRESS and resting-state functional magnetic resonance imaging, we quantified brain GSH and glutamate in the medial prefrontal cortex (mPFC) and precuneus and explore relationships between the GSH levels and intrinsic neuronal activity as well as clinical symptoms among the three groups of healthy controls (HCs, N=30), major depressive disorder (MDD, N=28), and obsessive-compulsive disorder (OCD, N=28). RESULTS: GSH concentrations were lower in both the mPFC and precuneus in both the MDD and OCD groups compared to HCs. In HCs, positive correlations were noted between the GSH and glutamate levels, and between GSH and fractional amplitude of low-frequency fluctuations (fALFF) in both regions. However, while these correlations were absent in both patient groups, they showed a weak positive correlation between glutamate and fALFF values. Moreover, GSH levels negatively correlated with depressive and compulsive symptoms in MDD and OCD, respectively. CONCLUSIONS: These findings suggest that reduced GSH levels and an imbalance between GSH and glutamate could increase oxidative stress and alter neurotransmitter signaling, leading to disruptions in GSH-related neurochemical-neuronal coupling and psychopathologies across MDD and OCD. Understanding these mechanisms could provide valuable insights into the underlying processes of these disorders, potentially becoming a springboard for future directions and advancing our knowledge of their neurobiological foundations.

Hereditary Patterns and Genetic Associations in Obsessive-Compulsive Disorder (OCD): Neuropsychiatric Insights, Genetic Influences, and Treatment Perspectives.

Obsessive-Compulsive Disorder (OCD), a prevalent neuropsychiatric condition, affects approximately 2%-3% of the global population. This paper provides an extensive overview of OCD, detailing its clinical manifestations, neurobiological underpinnings, and therapeutic approaches. It examines OCD's classification shift in the DSM-5, the role of the cortico-striatothalamo- cortical pathway in its development, and the various factors contributing to its etiology, such as genes, environmental factors, and genetic predispositions. The challenges in diagnosing OCD and the effectiveness of both psychological and pharmacotherapeutic treatments are discussed. The paper also highlights the significant overlap between OCD and other mental health disorders, emphasizing its impact on global disability. Moreover, the role of genetic factors in OCD, including twin studies and gene association studies, is elaborated, underscoring the complex interplay of hereditary and environmental influences in its manifestation. The review further delves into the polygenic nature of OCD, illustrating how multiple genes contribute to its development, and explores the implications of genetic studies in understanding the disorder's complexity. Additionally, this research study delves into the concept of polygenic inheritance in complex diseases, highlighting the role of multiple genes in increasing OCD risk. A Genome-wide Association Study (GWAS) is employed to assess Single Nucleotide Polymorphisms (SNPs) to unearth genetic associations with OCD. This comprehensive analysis provides valuable insights into OCD's genetic landscape, paving the way for enhanced diagnostic approaches and treatment modalities.

Off-Label Use of Naltrexone in Pica and Other Compulsive Behaviors: A Report of Two Cases.

Pica is known to the medical community as an eating disorder in which individuals may ingest non-food items due to a nutritional deficiency and cause unintentional physical harm to themselves. This article discusses the cases of children with pica in addition to other comorbidities such as trichotillomania, depression, autism, and anxiety. Both patients were trialed on typical first-line treatments to address pica symptoms, including antidepressants, psychotherapy, and neurology consults, which were ineffective in treating pica symptoms. The introduction of naltrexone resulted in significant improvements, including decreased pica symptoms and improvements in depression, anxiety, and overall behaviors. These effects of naltrexone were further bolstered by the effects that occurred when both patients discontinued naltrexone for some time.

Advances in Pediatric Obsessive-Compulsive Disorder (OCD) Treatment: A Comprehensive Narrative Review.

Obsessive-compulsive disorder (OCD), characterized by persistent, intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), can significantly impact a child's daily functioning, academic performance, and overall quality of life. As the prevalence of pediatric OCD continues to rise, there is a critical demand for evidence-based treatments that not only alleviate symptoms but also enhance the quality of life for affected children and adolescents. By identifying gaps in knowledge and suggesting directions for future research, this narrative review contributes to the ongoing discourse on pediatric OCD treatments. Ultimately, the synthesis of evidence aims to enhance our understanding and inform best practices in the compassionate and effective management of OCD in children and adolescents. The aim of this study is to provide a comprehensive overview of current trends and emerging strategies in the treatment of pediatric obsessive-compulsive disorder (OCD) and highlights the significance of tailoring treatment approaches to individual patient needs, considering factors such as symptom severity and treatment response. Concentrating on interventions supported by empirical evidence, the review delves into cognitive-behavioral therapy (CBT), pharmacotherapy, the synergistic effects of these modalities, and inventive therapeutic approaches, all while considering the distinctive developmental aspects pertinent to pediatric populations. We conducted this review by searching for titles in the PubMed database from 2013 to present. Our comprehensive literature review focused on advancements in treating pediatric OCD, using keywords like "Obsessive-compulsive disorder," "Pediatric," "treatment," "CBT," "SSRI," "Pharmacotherapy," and "combination therapy." While both pharmacotherapy and CBT show individual efficacy, the combination of these approaches appears to be more effective, especially for medication non-responders with no prior exposure to CBT, despite some mixed findings. These findings contribute significantly to the ongoing discussion on optimizing combined therapy strategies tailored to the complexities of pediatric OCD.

Investigation of the psychometric properties of the Toronto Alexithymia Scale in men with and without compulsive sexual behavior.

Background: Previous studies have provided initial evidence supporting the association between compulsive sexual behavior (CSB) and alexithymia, but these studies did not investigate the psychometric property of a measure of alexithymia in individuals with CSB, which is necessary. Aim: This study investigated the factor analysis, reliability, and construct validity of the Toronto Alexithymia Scale (TAS) in men with CSB and control individuals. Methods: This cross-sectional study included 418 participants (304 individuals with CSB and 114 control individuals) who underwent a semi-structured psychiatric interview and completed the following instruments: the Sexual Compulsivity Scale, Hypersexual Disorder Screening Inventory, Beck Anxiety Inventory, Beck Depression Inventory, TAS, and Barratt Impulsiveness Scale. The eligible participants were men 18 years of age or older who were literate and residing in Brazil. Individuals who met the diagnostic criteria for Goodman's criteria for sex addiction were subsequently assessed for the excessive sexual drive (International Classification of Diseases-Tenth Revision F52.7) criteria. Those who met this second criteria were considered individuals with CSB. Participants who did not reach this point were considered control individuals. We conducted factor analysis, reliability analysis (internal consistency and temporal stability), and discriminant and construct validity analyses. Outcomes: The outcomes included the TAS total score and scores on TAS factors 1, 2, 3, and 4. Results: The extracted factors explained 44% of the variance in the TAS. Factor 1 explained 21%, but 3 items (items 2, 9, and 21) did not load onto this factor. The Cronbach's alpha was 0.83, and the reproducibility (intraclass correlation coefficient) was 0.70. The TAS can differentiate between individuals with CSB and control individuals. The different forms of validity were demonstrated through correlations between factors 1 to 4 and the total score, as well as with impulsivity, hypersexuality, sexual compulsivity, and depression. Surprisingly, anxiety was only weakly correlated with factors 1 and 2. Moreover, the TAS-4 score was not correlated with impulsivity. Clinical Implications: The TAS can be used in clinical practice to identify men with difficulties in recognizing subjective experiences, and proper interventions can subsequently be provided to these patients to increase their treatment efficacy. Strengths and Limitations: Various dimensions of alexithymia covary with other key psychopathological symptoms of CSB. This study examined a convenience sample. The results cannot be generalized to the broader population. Factors 3 and 4 presented low internal consistency (0.50). Conclusion: In general, TAS presented good psychometric properties in a sample mainly composed of individuals with CSB.

Cerebrospinal fluid characteristics of patients presenting for evaluation of pediatric acute-neuropsychiatric syndrome.

Objectives: This study characterizes cerebral spinal fluid (CSF) indices including total protein, the albumin quotient, IgG index and oligoclonal bands in patients followed at a single center for pediatric acute-neuropsychiatric syndrome (PANS) and other psychiatric/behavioral deteriorations. Methods: In a retrospective chart review of 471 consecutive subjects evaluated for PANS at a single center, navigational keyword search of the electronic medical record was used to identify patients who underwent lumbar puncture (LP) as part of the evaluation of a severe or atypical psychiatric deterioration. Psychiatric symptom data was ascertained from parent questionnaires and clinical psychiatric evaluations. Inclusion criteria required that subjects presented with psychiatric deterioration at the time of first clinical visit and had a lumbar puncture completed as part of their evaluation. Subjects were categorized into three subgroups based on diagnosis: PANS (acute-onset of severe obsessive compulsive disorder (OCD) and/or eating restriction plus two other neuropsychiatric symptoms), autoimmune encephalitis (AE), and "other neuropsychiatric deterioration" (subacute onset of severe OCD, eating restriction, behavioral regression, psychosis, etc; not meeting criteria for PANS or AE). Results: 71/471 (15.0 %) of patients underwent LP. At least one CSF abnormality was seen in 29% of patients with PANS, 45% of patients with "other neuropsychiatric deterioration", and 40% of patients who met criteria for autoimmune encephalitis. The most common findings included elevated CSF protein and/or albumin quotient. Elevated IgG index and IgG oligoclonal bands were rare in all three groups. Conclusion: Elevation of CSF protein and albumin quotient were found in pediatric patients undergoing LP for evaluation of severe psychiatric deteriorations (PANS, AE, and other neuropsychiatric deteriorations). Further studies are warranted to investigate blood brain barrier integrity at the onset of the neuropsychiatric deterioration and explore inflammatory mechanisms.

Religious scrupulosity and early maladaptive schemas: a network analysis.

Scrupulosity is treated as a particular presentation of the symptomatology characteristic for obsessive-compulsive disorder (OCD). However, typical treatment of OCD (e.g. cognitive-behavioral therapy) is less effective in the case of religious scruples. Recently, schema therapy has appeared as an alternative effective treatment in obsessive-compulsive symptomatology. The present study investigated the associations between early maladaptive schemas (EMSs) and scrupulosity in a non-clinical sample of 376 poles. The participants assessed their EMSs with the Young Schema Questionnaire 3 - Short Form and their scrupulosity with the Pennsylvania Inventory of Scrupulosity. We used network analysis to control for the EMS interconnectivity. We showed that accounting for the interactions within the EMSs, three schemas, namely, Punitiveness, Subjugation, and Enmeshment/Undeveloped Self, were positively correlated with scrupulosity. Given the central position of the Negativity/Pessimism schema in the examined network, we suggested that activation of this schema could be indirectly correlated to scruples via an escalation of activation to the Punitiveness, Subjugation, and Enmeshment schemas. The findings suggest that dependency and fear of rejection problems (present in Subjugation and Enmeshment EMSs) and over-compensation by perfectionism (present in Punitiveness EMS) could be addressed in the treatment of scruples.

Deep brain stimulation for obsessive compulsive disorder: the functional neurosurgeon armamentarium.

Deep brain stimulation (DBS) is a neurosurgical procedure that utilizes implanted electrodes and electrical stimulation for the treatment of neurological disorders. In cases where patients present with severe functional impairment while being refractory to less invasive treatment options, DBS is considered "gold standard." Still, DBS-related work is still widely under investigation, with ethical issues arising that may impact a patient's physical and psycho-social status. These include patient selection, informed consent, patient autonomy, pre-operation counseling and professional psycho-social preparation and follow-up support. Bioethicists and philosophers have increasingly worked together with in clinicians and researchers to identify, address and present ethical consideration in both clinical practice and research to balance the risk-benefit ratio in DBS treatment for obsessive-compulsive disorder.

Dual stimulation with iTBS-cTBS treatment in postpartum obsessive-compulsive disorder: a case report.

AIM OF THE STUDY: This study aimed to present a case of intermittent theta-burst stimulation (iTBS) and continuous theta-burst stimulation (cTBS) dual stimulation for the treatment of postpartum obsessive-compulsive disorder (OCD). The objective was to provide a referenceable therapy in cases where medication and psychotherapy treatment are not preferred or contraindicated. This case further emphasized the importance of non-invasive neuromodulation techniques in improving the condition of postpartum OCD patients. MATERIALS AND METHODS: A 32-year-old female was diagnosed with OCD 2 months after delivery. The patient refused to take medication and psychotherapy due to concerns that it would interfere with the infant's breastfeeding. Subsequently, a 2-week combined iTBS and cTBS treatment was carried out. The patient's obsessive-compulsive symptoms, anxiety, and depression improved. There were no significant adverse effects during the treatment, and the treatment effect remained 2 weeks after the end of the treatment. CONCLUSION: This clinical case provides evidence that the combined iTBS and cTBS treatment can potentially effectively alleviate obsessive-compulsive symptoms in the short term. Notably, this therapeutic approach may offer a promising solution for postpartum OCD patients, as it addresses practical concerns such as medication safety for breastfeeding mothers and the specific needs of this population. To further establish the efficacy of this combined therapy, future randomized controlled trials with large samples and long-term follow-up are warranted to validate its therapeutic potential.

Exploring functional connectivity in large-scale brain networks in obsessive-compulsive disorder: a systematic review of EEG and fMRI studies.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition that is difficult to treat due to our limited understanding of its pathophysiology. Functional connectivity in brain networks, as evaluated through neuroimaging studies, plays a pivotal role in understanding OCD. While both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been extensively employed in OCD research, few have fully synthesized their findings. To bridge this gap, we reviewed 166 studies (10 EEG, 156 fMRI) published up to December 2023. In EEG studies, OCD exhibited lower connectivity in delta and alpha bands, with inconsistent findings in other frequency bands. Resting-state fMRI studies reported conflicting connectivity patterns within the default mode network (DMN) and sensorimotor cortico-striato-thalamo-cortical (CSTC) circuitry. Many studies observed decreased resting-state connectivity between the DMN and salience network (SN), implicating the 'triple network model' in OCD. Task-related hyperconnectivity within the DMN-SN and hypoconnectivity between the SN and frontoparietal network suggest OCD-related cognitive inflexibility, potentially due to triple network dysfunction. In conclusion, our review highlights diverse connectivity differences in OCD, revealing complex brain network interplay that contributes to symptom manifestation. However, the presence of conflicting findings underscores the necessity for targeted research to achieve a comprehensive understanding of the pathophysiology of OCD.

Assessing the effectiveness of high-definition transcranial direct current stimulation for treating obsessive-compulsive disorder: Results from a randomized, double-blind, controlled trial.

OBJECTIVE: Characterized by its disabling nature, obsessive compulsive disorder (OCD) affects individuals profoundly, with nearly 40% of patients showing resistance to initial treatment methods. Despite being safe and easily accessible, transcranial direct current stimulation (tDCS) lacks extensive substantiation supporting its efficacy in treating OCD. The objective of this study was to evaluate how cathodal high-definition transcranial direct current stimulation (HD-tDCS) applied to the right orbitofrontal cortex affected patients with OCD in terms of efficacy. METHOD: 47 patients with OCD were enrolled. They were randomly allocated to active or sham stimulation groups, and underwent HD-tDCS stimulation treatment for 2 weeks. The central electrode located in the right orbitofrontal cortex region was cathodic. The severity of the patients' obsessive-compulsive symptoms, depression and anxiety were assessed before and after treatment. RESULT: Out of the total, 44 patients concluded the treatment, comprising 23 participants from the active stimulation group and 21 from the sham stimulation group. Notably, substantial reductions in symptoms related to OCD, depression, and anxiety were exhibited in both groups. With a response rate of 26.1% in the active stimulation group and 23.8% in the sham stimulation group, there was no significant difference in efficacy observed. Furthermore, the reduction in depression and anxiety symptoms at the conclusion of the treatment was not notably superior in the active stimulation group. CONCLUSION: This study provided evidence for the acceptability and safety of HD-tDCS. Nevertheless, the study did not reveal notable clinical effectiveness of tDCS in addressing moderate to severe OCD in comparison to the sham stimulation group.

Statistical predictors of the co-occurrence between gambling disorder and problematic pornography use.

Co-occurrence between gambling disorder (GD) and other mental disorders is common, but its association with problematic pornography use (PPU) remains unexplored. This study aimed to investigate relationships between sociodemographic variables, personality measures, psychopathology, emotional regulation, and impulsivity and the co-occurrence of GD and PPU using structural equation modeling (SEM). The sample consisted of 359 adults seeking treatment for GD. The short version of the Problematic Pornography Consumption Scale (PPCS-6) identified patients with GD + PPU. Psychopathology, impulsivity, emotional regulation, and personality were also assessed. Higher impulsivity levels statistically predicted co-occurrence between GD and PPU. Impulsivity mediated the relationship between younger age, maladaptive personality features, and emotional dysregulation and co-occurrence. Psychopathological distress did not directly associate with GD + PPU co-occurrence. Impulsivity relates importantly to the co-occurrence of GD and PPU. Younger age, maladaptive personality, and emotional dysregulation contribute to increased impulsivity levels and co-occurrence. The findings highlight the importance of addressing impulsivity in understanding and treating co-occurring GD and PPU.

White matter changes after Gamma Knife Capsulotomy in patients with intractable obsessive-compulsive disorder.

Background: Anterior capsulotomy is one of the therapeutic options for refractory obsessive-compulsive disorder (OCD). Safety and efficacy of Gamma Knife Capsulotomy (GKC) have been demonstrated in the past. Objective: To characterize changes induced by GKC using a fixel-based analysis (FBA) and possible predictors of efficacy. Methods: Patients with OCD refractory to other therapies underwent bilateral GKC with 120 Gy as a maximum dose on the anterior limb of the internal capsule (ALIC). The clinical outcome was percent reduction in Yale- Brown Obsessive-Compulsive Scale (Y-BOCS). White Matter changes were analyzed using fixel-based analysis (FBA) for fibre density (FD), fibre-bundle cross-section (FC) and the combination of the two (FDC). Results: Seven patients underwent GKC. Median follow-up was 13 months (range 12-58 months). Mean (±SD) decrease in Y-BOCS score at last follow-up was 61 % ± 35 % with five patients considered as responders. FBA showed a symmetric FD reduction in the ALIC with extension to the anterior fronto-thalamic radiation; a reduction of FC along the superior longitudinal fasciculus (SLF) in both hemispheres with a predominance in the left one. Reductions in FDC were detected predominantly in the right hemisphere, with a similar pattern to FD reductions and associated with a positive correlation (p < 0.05) between Y-BOCS reduction and fibres passing in the ventral part. Conclusions: GKC is safe and efficient in reducing OCD severity in selected patients. Changes induced in white matter by GKC extend over the ALIC. Reduction of fibres passing the ventral part of the right sided ALIC correlates with better results.

Structure, network analysis, psychometric properties and clinical utility of the self-absorption scale in China.

BACKGROUND: Self-absorption refers an excessive, persistent, and rigid preoccupation with information regarding the self. This study aims to introduce the Self-Absorption Scale (SAS) into China with an assessment of its latent variable structure, network structure, psychometric properties, and clinical utility in a nonclinical Chinese sample. METHODS: 209 participants completed the translated SAS as well as the Short General Health Questionnaire (GHQ-12), rumination subscale of the Rumination-Reflection Questionnaire (RRQ), the Mindful Attention Awareness Scale (MAAS), the Private Self-Consciousness Scale (PrSCS), the Obsessive-Compulsive Inventory-Revised (OCI-R) and the Dissociative Experiences Scale (DES-II). In addition, 30 respondents completed the Chinese version of the SAS and retested it 2 weeks later. RESULTS: The Chinese version of the SAS (CH-SAS) had a desirable two-correlated-factor structure with the reverse scored item removed, which was invariant across different genders. The core items in the network structure of the CH-SAS were related to excessive self-immersion, uncontrollability and anxiety aspects of self-absorption. The Cronbach's alpha coefficient for the CH-SAS was 0.903 while the McDonald's omega coefficient was 0.916 and the test-retest reliability was 0.908. The CH-SAS and its two subscales had moderate positive correlations with the rumination subscale of the RRQ (ranging from 0.474 to 0.616; p < .001) and the GHQ-12 (ranging from 0.479 to 0.538; p < .001), and moderate negative correlations with the MAAS (ranging from - 0.413 to - 0.360; p < .001). The PrSCS has almost no correlation with the CH-SAS and PrSAS (p > .05), and its correlation with the PubSAS was significant at the 0.05 level, with a remarkably low correlation coefficient (r = .157). The hierarchical regression analysis suggested that the CH-SAS can significantly predict the severity of OCD beyond factors such as depression, anxiety, rumination, dissociation, and mindful attention awareness. CONCLUSIONS: The CH-SAS demonstrates excellent reliability, including internal consistency and test-retest reliability. Additionally, it exhibits favorable structural validity, as well as strong evidence of convergent and divergent validity. Furthermore, the self-absorption measured using the CH-SAS contributed significantly to the prediction of OCD beyond other relevant psychological factors, suggesting its clinical utility.

Differential impact of pegfilgrastim, a recombinant human granulocyte colony stimulating factor, on the neutrophil count of male and female deer mice (Peromyscus maniculatus bairdii).

BACKGROUND: An increasing body of research implicates inflammatory processes, including alterations in the neutrophil-lymphocyte ratio (NLR), in the pathophysiology of psychiatric illness. The deer mouse (Peromyscus maniculatus bairdii) is commonly studied for its naturalistic expression of compulsive-like behaviour. Towards future efforts to gain an understanding of how innate and adaptive immune processes might be involved in this model, we aimed to study the effects of pegfilgrastim, a pegylated recombinant human granulocyte colony-stimulating factor (g-CSF) analogue, on the NLR of both male and female deer mice. METHODS: Briefly, 54 deer mice (equally distributed between sexes) were exposed to a single injection with either control or pegfilgrastim (0.1 or 1 mg/kg) (n = 18 per group). Six mice of each group (three per sex) were euthanized on days two, four and seven post-administration, their blood collected and the NLR calculated. Data were analysed by means of ordinary three-way ANOVA, followed by Bonferroni post-hoc testing. RESULTS: Irrespective of dose, pegfilgrastim resulted in higher NLR values in mice of both sexes at days four and seven of testing. However, female mice exposed to the higher dose, presented with significantly higher NLR values irrespective of time, compared to male mice exposed to the same. CONCLUSION: The data generated from this work highlight important dose- and sex-specific aspects of pegfilgrastim with female mice showing heighted elevation of the NLR in response to high-dose pegfilgrastim administration only. Since the innate immune components of male and female deer mice is differentially sensitive to g-CSF stimulation, our results provide a useful basis for further study of sex-specific immunological processes in deer mice.

Late development of OCD-like phenotypes in Dlgap1 knockout mice.

RATIONALE: Despite variants in the Dlgap1 gene having the two lowest p-value in a genome-wide association study of obsessive compulsive disorder (OCD), previous studies reported the absence of OCD-like phenotypes in Dlgap1 knockout (KO) mice. Since these studies observed behavioral phenotypes only for a short period, development of OCD-like phenotypes in these mice at older ages was still plausible. OBJECTIVE: To examine the presence or absence of development of OCD-like phenotypes in Dlgap1 KO mice and their responsiveness to fluvoxamine. METHODS AND RESULTS: Newly produced Dlgap1 KO mice were observed for a year. Modified SHIRPA primary screen in 2-month-old homozygous mutant mice showed only weak signs of anxiety, stress conditions and aggression. At older ages, however, these mutant mice exhibited excessive self-grooming characterized by increased scratching which led to skin lesions. A significant sex difference was observed in this scratching behavior. The penetrance of skin lesions reached 50% at 6-7 months of age and 90% at 12 months of age. In the open-field test performed just after the appearance of these lesions, homozygous mutant mice spent significantly less time in the center, an anxiety-like behavior, than did their wild-type and heterozygous littermates, none and less than 10% of which showed skin lesions at 1 year, respectively. The skin lesions and excessive self-grooming were significantly alleviated by two-week treatment with fluvoxamine. CONCLUSION: Usefulness of Dlgap1 KO mice as a tool for investigating the pathogenesis of OCD-like phenotypes and its translational relevance was suggested.

Long-term safety and efficacy of focused ultrasound capsulotomy for obsessive-compulsive disorder and major depressive disorder.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluate the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). METHODS: This phase I single center open label study recruited treatment-resistant OCD and MDD. Outcomes were measured 6mo, 12mo, and 18-24months (long-term) after MRgFUS capsulotomy. Neuropsychological testing and neuroimaging were conducted at baseline and 12mo postoperatively. The primary outcome was safety. The secondary outcome was clinical response, defined for OCD as ≥35% improvement in Yale-Brown obsessive-compulsive scale (YBOCS) scores, and for MDD as a ≥50% reduction in the Hamilton Depression Rating Scale (HAMD-17) scores, compared to baseline. RESULTS: No serious adverse effects were registered. In patients with OCD (n=15), baseline YBOCS scores (31.9±1.2) were significantly reduced by 23% (p=0.01) at 6mo and 35% (p<0.0001) at 12mo. In patients with MDD (n=12), a 26% and 25% non-significant reduction in HAMD-17 scores (baseline 24.3±1.2) was observed at 6mo and 12mo, respectively. Neuropsychological testing revealed no negative effects of capsulotomy. In the OCD and MDD cohorts we found a correlation between clinical outcome and lesion laterality, with more medial left (OCD, p=0.08) and more lateral right (MDD, p<0.05) placed lesions being respectively associated with a stronger response. In the MDD cohort, more ventral tracts appeared to be associated with a poorer response. CONCLUSIONS: MRgFUS capsulotomy is safe in patients with OCD and MDD and particularly effective in the former population.

Exploring the impact of pediatric OCD on family impairment: A consideration of parent, sibling, and affected-child perspectives.

BACKGROUND: Previous studies have examined the perspectives of both affected children/adolescents and their parents on family functioning impacts of obsessive-compulsive disorder (OCD). While siblings play an integral role within the family system, their perspectives have been largely overlooked in the literature. This study examined sibling, parent, and child perspectives of family functioning in pediatric OCD and assessed demographic and clinical factors associated with family functioning. METHODS: Participating families were identified from a larger research registry of 398 patients referred between 2012 and 2020 to the Provincial OCD Program. A total of 185 families who provided data on family functioning from the perspectives of OCD-affected children, siblings and parents were included for study. All family members completed the OCD Family Functioning scale. RESULTS: The extent of perceived impairment differed by family member type, with parents reporting the greatest impacts, followed by OCD-affected children, and then siblings. Predictors of OCD-imposed family dysfunction included family accommodation from all perspectives, clinician-reported child OCD severity, and family blame from parent perspectives. LIMITATIONS: Data are cross-sectional, and we cannot conclude that the observed associations reflect causal effects. Missing data were evident and differed by variable item and family member type. CONCLUSIONS: By providing sibling perspectives within the same family unit, this study expands upon previous findings that accommodation predicts family impairment from parent and child perspectives. Our study highlights factors relevant to family-based interventions in the treatment of pediatric OCD. Clinicians should be aware of the ongoing impacts OCD has on all family members.

A preliminary study of factors associated with accommodation of obsessive-compulsive symptoms by romantic partners.

OBJECTIVES: The accommodation of symptoms of obsessive-compulsive disorder (OCD) by loved ones is highly prevalent and impactful on treatment outcomes; however, little is known about factors that influence accommodation by romantic partners of OCD sufferers. The aim of this preliminary investigation was to explore such correlates. METHODS: A community sample of 50 patients self-identifying with OCD (Mage = 29.3; SD = 9.3; 74% female) and 20 individuals self-identifying as the partner of someone with OCD (Mage = 32.1; SD = 12.4; 65% female) participated in this study via an online questionnaire. RESULTS: Associations were found between partner accommodation of OCD and a range of obsessions and compulsions across the patient and partner samples, as well as patient-reported symptom severity, functional impairment and negative emotion states. Neuroticism was also positively associated with partner accommodation in the patient sample but did not contribute to its prediction over and above other known correlates of family accommodation. In the partner sample, extraversion was found to be a unique negative correlate of partner accommodation. CONCLUSIONS: These findings highlight the vital role both patient and partner factors play in the accommodation of OCD behaviours by romantic partners and the importance of involving loved ones in the treatment of individuals with OCD.