Amelioration of obsessive-compulsive disorder by intracellular acidification of cortical neurons with a proton pump inhibitor.

Obsessive-compulsive disorder (OCD) is a highly prevalent neuropsychiatric disorder poorly controlled with pharmacological treatment because of the wide variation in symptom patterns. We analysed real-world data on adverse self-reports and insurance claims to identify a novel therapeutic target for OCD. We found that dopamine D2 receptor (D2R) agonists increased the incidence of OCD-like symptoms, which were suppressed by the concomitant use of proton pump inhibitors (PPIs). Further, OCD-like repetitive and habitual behaviours were observed in mice repeatedly injected with a D2R agonist, quinpirole. However, these abnormalities were suppressed by short-term PPI treatment. In quinpirole-treated mice, PPI inhibited pyramidal neuron hyperactivity in the lateral orbitofrontal cortex, a region where the P-type proton pump gene Atp4a is abundantly expressed. In primary cultured cortical neurons, short-term PPI treatment lowered intracellular pH and decreased firing activity, which was mimicked by Atp4a knockdown. Our findings show that inhibition of P-type proton pumps may be a novel therapeutic strategy for OCD.

Obsessive-compulsive disorder following severe traumatic brain injury.

Obsessive-compulsive disorder (OCD) as a consequence of severe traumatic brain injury (TBI) has been reported in a limited number of case studies. Informed by CARE guidelines, we present the case of a boy in his late adolescence who sustained a severe TBI from a motor vehicle crash. His injuries required a prolonged stay in the hospital, including 3 weeks in the intensive care unit and a craniotomy to evacuate a large subdural haematoma. Obsessive-compulsive behaviours were first observed on discharge from the hospital and became worse over time. Compulsive behaviours were considered in light of a neuropsychological examination, and a diagnosis of OCD was attained. Sertraline was prescribed and effectively reduced the severity of OCD symptoms. Given the challenges comorbid conditions can pose to neurorehabilitation, a better understanding of patterns in OCD symptoms and brain lesions among reported cases will help guide the diagnosis of OCD among individuals with severe TBI.

Melatonin-mediated IGF-1/GLP-1 activation in experimental OCD rats: Evidence from CSF, blood plasma, brain and in-silico investigations.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition characterized by intrusive, repetitive thoughts and behaviors. Our study uses a validated 8-OH-DPAT-induced experimental model of OCD in rodents. We focus on the modulatory effects of Insulin-like growth factor-1 (IGF-1) and glucagon-like peptide-1 (GLP-1), which are linked to neurodevelopment and survival. Current research investigates melatonin, a molecule with neuroprotective properties and multiple functions. Melatonin has beneficial effects on various illnesses, including Alzheimer's, Parkinson's, and depression, indicating its potential efficacy in treating OCD. In the present study, we employed two doses of melatonin, 5 mg/kg and 10 mg/kg, demonstrating a dose-dependent effect on 8-OH-DPAT-induced rat changes. In addition, the melatonin antagonist luzindole 5 mg/kg was utilized to compare and validate the efficacy of melatonin. In-silico studies alsocontribute to understanding the activation of IGF-1/GLP-1 pathways by melatonin. Current research indicates restoring neurochemical measurements on various biological samples (brain homogenates, CSF, and blood plasma) and morphological and histological analyses. In addition, the current research seeks to increase understanding of OCD and investigate potential new treatment strategies. Therefore, it is evident from the aforementioned research that the protective effect of melatonin can serve as a strong basis for developing a new OCD treatment by upregulating IGF-1 and GLP-1 levels. The primary focus of current study revolves around the examination of melatonin as an activator of IGF-1/GLP-1, with the aim of potentially mitigating behavioral, neurochemical, and histopathological abnormalities in an experimental model of obsessive-compulsive disorder caused by 8-OH-DPAT in adult Wistar rats.

COVID-19-related intrusive thoughts and associated ritualistic behaviors.

This study evaluated COVID-19-related intrusive thoughts and associated ritualistic behaviors (CITRB). From March to May 2020, 1,118 Chinese high school students, college students, psychiatric outpatients, and community members completed a survey assessing CITRB, generalized anxiety, depression, somatization, obsessive-compulsive symptoms, and pandemic-related disruptions. Overall, participants reported mild to moderate CITRB, although certain thoughts/behaviors were more frequently endorsed, such as repeatedly telling others to take precautions against COVID-19 and checking COVID-19-related news. Being male, younger, a health-care worker, or in isolation/quarantine was associated with CITRB severity in community members. Obsessive-compulsive symptom severity, depression, somatic symptoms, and anxiety were associated with CITRB severity, although only obsessive-compulsive symptoms were uniquely associated with CITRB. This study provided evidence for the construct of CITRB, which may help mental health providers identify the nature and sources of COVID-19-related distress for some individuals as well as serve as a framework for evaluating obsessive-compulsive symptoms specific to large-scale crises.

In search of environmental risk factors for obsessive-compulsive disorder: study protocol for the OCDTWIN project.

BACKGROUND: The causes of obsessive-compulsive disorder (OCD) remain unknown. Gene-searching efforts are well underway, but the identification of environmental risk factors is at least as important and should be a priority because some of them may be amenable to prevention or early intervention strategies. Genetically informative studies, particularly those employing the discordant monozygotic (MZ) twin design, are ideally suited to study environmental risk factors. This protocol paper describes the study rationale, aims, and methods of OCDTWIN, an open cohort of MZ twin pairs who are discordant for the diagnosis of OCD. METHODS: OCDTWIN has two broad aims. In Aim 1, we are recruiting MZ twin pairs from across Sweden, conducting thorough clinical assessments, and building a biobank of biological specimens, including blood, saliva, urine, stool, hair, nails, and multimodal brain imaging. A wealth of early life exposures (e.g., perinatal variables, health-related information, psychosocial stressors) are available through linkage with the nationwide registers and the Swedish Twin Registry. Blood spots stored in the Swedish phenylketonuria (PKU) biobank will be available to extract DNA, proteins, and metabolites, providing an invaluable source of biomaterial taken at birth. In Aim 2, we will perform within-pair comparisons of discordant MZ twins, which will allow us to isolate unique environmental risk factors that are in the causal pathway to OCD, while strictly controlling for genetic and early shared environmental influences. To date (May 2023), 43 pairs of twins (21 discordant for OCD) have been recruited. DISCUSSION: OCDTWIN hopes to generate unique insights into environmental risk factors that are in the causal pathway to OCD, some of which have the potential of being actionable targets.

Contemporary Role of Stereotactic Radiosurgery for Psychiatric Disorders.

Psychiatric disorders are the hidden pandemic of the current century. Despite major advances in medical management, the options for treatment are still limited. Neurosurgical intervention is effective for certain refractory psychiatric illnesses and the options range from stimulation surgeries to precise disconnection procedures influencing the neuronal network. Literature regarding stereotactic radiosurgery (SRS) is now enriched with successful treatment of obsessive compulsive disorder, major depression disorder, and anorexia nervosa. These procedures by reducing compulsions, obsessions, depression, and anxiety, improve substantially the quality of life for patients with a good safety profile. It is a valid treatment alternative for a selected group of patients who otherwise have no therapeutic options for whom the neurosurgical intervention is the only hope. It is also cost effective and highly reproducible among specialists. These procedures are adjuvant to the medical and behavioural treatment of psychiatric disorders. In this study the Contemporary role of Stereotactic radiosurgery is reviewed starting with relevant history of psychosurgery followed by individual psychiatric disorders.

Mental health symptoms among those affected by Huntington's disease: A cross-sectional study.

BACKGROUND: Although cognitive and motor symptoms of Huntington's disease (HD) are associated with disease progression, the underlying causes of psychological symptoms are not as clearly understood. Recent evidence suggests that some mental health difficulties experienced by people with HD are shared by noncarriers within HD families. Accordingly, there is a need to evaluate potential systemic contributors to HD mental distress, to support meaningful interventions for psychological symptoms in people with HD and affected families. METHOD: We used short-form Problem Behaviors Assessment mental health symptom data from the international Enroll-HD data set to characterize mental health symptoms across eight HD groups: Stages 1-5, premanifest and genotype-negative individuals, and family controls (n = 8567) using chi-square analysis with post hoc comparisons. RESULTS: We identified that people with later-stage HD (Stages 2-5) had significantly higher apathy, obsessive-compulsiveness, and (from Stage 3) disorientation than the remaining groups at a medium effect size, and that these findings largely held across three measure administrations over time. CONCLUSIONS: These findings highlight the critical symptoms in manifest HD from Stage 2 onward, but also demonstrate that crucial symptoms such as depression, anxiety, and irritability are present across HD-affected groups (including noncarriers of the gene expansion). The outcomes highlight a need for specific clinical management of later-stage HD psychological symptoms, and for systemic support across affected families.

Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder and Tic Disorder: A Quick Review.

Repetitive transcranial megnetic stimulation (rTMS) has been widely used in patients with psychiatric disorders. Previous studies revealed good efficacy of rTMS for patients with obsession-compulsive disorder (OCD) and Tic disorder (TD). OCD and TD are closely related and considered to etiologically overlap. Patients with the co-occurrence of OCD and TD are often identified. Therefore, we conducted a quick review of rTMS for the treatment of these two diseases to compare the similarities and differences of rTMS for OCD and TD, which might provide an indication for the treatment of the co-occurrence of OCD and TD. We searched articles published in PubMed, Wanfang, and Web of Science from January 2001 to January 2022. Both inclusion criteria and exclusion criteria were developed to identify the relevant included studies. Data on the frequency, target area, sample size, and number of males, especially the rTMS treatment procedure or parameters, were extracted in the included studies. We included 26 studies on OCD and 12 studies on TD in this quick review. A total of 996 participants were included. Based on the review of the included studies, lowfrequency rTMS might be used more than high-frequency rTMS, and the supplementary motor area (SMA) might show better efficacy than the dorsolateral prefrontal cortex (DLPFC) in OCD. For patients with TD, low-frequency rTMS located in the SMA might show good efficacy both in OCD and TD. Our quick review elaborated the treatment efficacy of rTMS for both patients with OCD and those with TD. It seems that the SMA is an important target choice for both OCD and TD patients. Low-frequency rTMS might be used more than high-frequency rTMS in both OCD and TD patients. In future studies, we should explore more about the efficacy of rTMS for patients with co-occurring OCD and TD, especially for the efficacy of targeted SMA with low frequency.

Continuous theta burst stimulation over the bilateral supplementary motor area in obsessive-compulsive disorder treatment: A clinical randomized single-blind sham-controlled trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) can cause substantial damage to quality of life. Continuous theta burst stimulation (cTBS) is a promising treatment for OCD patients with the advantages of safety and noninvasiveness. OBJECTIVE: The present study aimed to evaluate the treatment efficacy of cTBS over the bilateral supplementary motor area (SMA) for OCD patients with a single-blind, sham-controlled design. METHODS: Fifty-four OCD patients were randomized to receive active or sham cTBS treatment over the bilateral SMA for 4 weeks (five sessions per week, 20 sessions in total). Patients were assessed at baseline (week 0), the end of treatment (week 4), and follow-up (week 8). Clinical scales included the YBOCS, HAMD24, HAMA14, and OBQ44. Three behavioral tests were also conducted to explore the effect of cTBS on response inhibition and decision-making in OCD patients. RESULTS: The treatment response rates were not significantly different between the two groups at week 4 (active: 23.1% vs. sham: 16.7%, p = 0.571) and week 8 (active: 26.9% vs. sham: 16.7%, p = 0.382). Depression and anxiety improvements were significantly different between the two groups at week 4 (HAMD24: F = 4.644, p = 0.037; HAMA14: F = 5.219, p = 0.028). There was no significant difference between the two groups in the performance of three behavioral tests. The treatment satisfaction and dropout rates were not significantly different between the two groups. CONCLUSIONS: The treatment of cTBS over the bilateral SMA was safe and tolerable, and it could significantly improve the depression and anxiety of OCD patients but was not enough to improve OCD symptoms in this study.

Stereotactic cingulotomy and capsulotomy for obsessive-compulsive disorders: Indications and comparative results.

Stereotactic cingulotomy and capsulotomy have been used to treat obsessive-compulsive disorders (OCD) and treatment-resistant depression since the 1950s-60s. To date, these surgical procedures have gained a number of advancements due to progress of neuroimaging and upgrading of stereotactic technique. The effectiveness of operations is related to the restoration of the normal level of limbic regulation in treated patients. In cases of OCD, capsulotomy is somewhat more effective, while cingulotomy has a more favorable safety profile. Moreover, clinical experience shows that these procedures may be efficient for management not only OCD itself, but for obsessive-compulsive symptoms in cases of other mental diseases, such as Tourette syndrome and schizophrenia, thus may be considered in carefully selected patients. An individualized treatment strategy, including staged stereotactic interventions, seems most promising for attainment of the best possible outcomes, and may allow to achieve socialization of 75% of the operated patients with minimal pharmacological support. Other potential stereotactic targets for management of OCD, which selection may depend on detail of clinical manifestation of disease, include thalamic nuclei, nucleus accumbens, globus pallidus, the amygdala, etc., and are currently under active evaluation, and their use is tremendously facilitated by the development of deep brain stimulation techniques. Nevertheless, cingulotomy and capsulotomy still remain highly relevant for treatment of patients with therapy-resistant mental disorders.

Perinatal Obsessive-Compulsive Disorder: Epidemiology, Phenomenology, Etiology, and Treatment.

PURPOSE OF REVIEW: We review recent evidence concerning the epidemiology, etiology, and treatment of obsessive-compulsive disorder (OCD) in the perinatal period. We examine studies reporting on rates of both new-onset OCD and exacerbation in both pregnancy and postpartum; explore both biological and psychosocial risk factors for the disorder; and review the latest evidence concerning treatment. RECENT FINDINGS: Evidence is limited in all areas, with rates of both OCD and subthreshold obsessive-compulsive symptoms varying widely across studies. Prevalence is likely higher in the perinatal period than in the general population. Clinical features in the perinatal period are more likely than at other times to concern harm to the child, with contamination and aggressive obsessions and cleaning and checking compulsions especially common. Research into the biological etiology is too limited at this time to be definitive. Both observational and randomized controlled trials support cognitive behavioral therapy with exposure and response prevention (CBT with ERP) as a first-line treatment, with limited evidence also supporting the use of selective serotonin reuptake inhibitors (SSRIs). Treatment considerations in the perinatal period must weigh the risks of treatment vs. the risks of untreated illness. Perinatal OCD is common and can be impairing. Clinical features differ somewhat compared to non-perinatal periods. Treatment does not differ from that used in the general population, though evidence pertaining specifically to the perinatal period is sparse.

Modern Gamma Knife radiosurgery for management of psychiatric disorders.

Psychiatric disorders result in great suffering of affected patients, who often have rather limited treatment options. In cases refractory to standard medical and behavioral therapy, interventional procedures may be the only feasible solution. The authors experience with Gamma Knife bilateral cingulotomy for treatment-resistant major depression disorder (5 cases) and anorexia nervosa (6 cases), and bilateral anterior capsulotomy for severe obsessive-compulsive disorder (10 cases) shows that such radiosurgical techniques may be applied both effectively and safely. During post-treatment follow-up, the vast majority of patients demonstrated gradual reduction of psychiatric symptoms and improvement of the quality of life, which was confirmed by results of regular neuropsychological testing and imaging examinations. No major side effect was observed in any case. More active application of radiosurgery (using standardized technique) for management of mental illnesses in various Gamma Knife centers worldwide should be encouraged.

Gamma Knife radiosurgery for obsessive compulsive disorder.

Gamma Knife radiosurgical capsulotomy has been performed for over 40 years as a rarely used surgical intervention for the treatment of obsessive-compulsive disorder. Over time, the procedure has evolved in many ways with most significant modifications being made in target location, number of isocenters and prescribed dose, subsequently producing changes in lesion size and geometry. Long-term clinical response data and adverse outcomes to the earlier empiric treatment parameters have resulted in shifting the target from its initial location within the midpoint of the anterior limb of internal capsule to a currently used point that includes its most ventral portion as well as the ventral striatum. This led to the contemporary Gamma Knife ventral capsulotomy procedure that focuses on ventral capsule/ventral striatum. Many of the early studies, despite demonstrating efficacy in some patients, were complicated by clinically relevant radiation-induced adverse effects. More recent studies have demonstrated strong efficacy with diminished adverse effects with well-placed lesions created at lower radiation doses. Advances in neuroimaging technology such as diffusion tensor imaging (DTI) based fiber tracking may provide further insight into precisely targeting of the ventral capsule/striatum based on patient-specific variations in white matter connectivity.

Postpartum Thoughts of Infant-Related Harm and Obsessive-Compulsive Disorder: Relation to Maternal Physical Aggression Toward the Infant.

Objective: Unwanted intrusive thoughts (UITs) of intentional infant-related harm are ubiquitous among new mothers and frequently raise concerns about infant safety. The purpose of this research was to assess the relation of new mothers' UITs of intentional, infant-related harm and obsessive-compulsive disorder (OCD) with maternal aggression toward the infant and to document the prevalence of maternal aggression toward the infant.Methods: From a prospective, province-wide, unselected sample of 763 English-speaking postpartum women, a total of 388 participants provided data for this portion of the research. Participants completed 2 questionnaires and interviews postpartum to assess UITs of infant-related harm, OCD (based on DSM-5 criteria), and maternal aggression toward the infant. Data for this research were collected from February 9, 2014, to February 14, 2017.Results: Overall, few participants (2.9%; 95% CI, 1.5% to 4.7%) reported behaving aggressively toward their infant. Participants who reported UITs of intentional, infant-related harm (44.4%; 95% CI, 39.2% to 49.7%) were not more likely to report aggression toward their newborn compared with women who did not report this ideation (2.6%; 95% CI, 0.9% to 5.8%; and 3.1%; 95% CI, 1.3% to 6.2%, respectively). The same was true for women with and without OCD (1.9%; 95% CI, 0.3% to 6.4%; and 3.5%; 95% CI, 1.8% to 6.0%), respectively.Conclusions: This study found no evidence that the occurrence of either UITs of intentional, infant-related harm or OCD is associated with an increased risk of infant harm. The prevalence of child abuse of infants in this sample (2.9%) is lower than reported in others (4%-9%). Findings provide critical and reassuring information regarding the relation between new mothers' UITs of intentional harm and risk of physical violence toward the infant.

Adjuvant Priming Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Obsessive-Compulsive Disorder: In Search of a New Paradigm!

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is used as a therapeutic option for obsessive-compulsive disorder (OCD) in both clinical and research settings. There has been no consensus with regard to target area and other parameters, although 1-Hz rTMS over the supplementary motor area (SMA) is found to be promising. Priming stimulation, which involves high-frequency followed by low-frequency rTMS, has been shown to enhance neural response to low-frequency rTMS. Hence, this study was conducted to investigate the effect of adjunctive priming rTMS over the SMA in treatment-resistant OCD. METHODS: Thirty patients with OCD who were symptomatic after an adequate selective serotonin reuptake inhibitor trial were randomized into 2 groups: one group receiving active priming stimulation (6-Hz rTMS at 80% resting motor threshold) followed by 1-Hz rTMS (priming rTMS group) and the other receiving sham stimulation followed by 1-Hz rTMS (rTMS-only group). Both groups received 10 sessions of such interventions for 2 weeks. Both the rater and patients were blind to the treatment allocation. Assessments were done using the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Clinical Global Impression-Improvement scale at baseline, 2 weeks, and 4 weeks. RESULTS: Both groups showed a significant improvement in all domains of psychopathology over time. The priming rTMS group was better than the rTMS-only group in reducing the Yale-Brown Obsessive Compulsive Scale compulsion score (P < 0.023) as well as scores of the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinical Global Impression-Improvement scale. None developed any adverse effects requiring medical attention. CONCLUSIONS: Priming rTMS over the SMA is safe and has favorable effects in OCD. It seems to have a predominant effect on the reduction of compulsions, presumably rectifying the impaired response inhibition in patients with OCD.

Eye movement as a biomarker of impaired organizational strategies during visual memory encoding in obsessive-compulsive disorder.

The symptoms of obsessive-compulsive disorder (OCD) are largely related to impaired executive functioning due to frontostriatal dysfunction. To better treat OCD, the development of biomarkers to bridge the gap between the symptomatic-cognitive phenotype and brain abnormalities is warranted. Therefore, we aimed to identify biomarkers of impaired organizational strategies during visual encoding processes in OCD patients by developing an eye tracking-based Rey-Osterrieth complex figure test (RCFT). In 104 OCD patients and 114 healthy controls (HCs), eye movements were recorded during memorization of the RCFT figure, and organizational scores were evaluated. Kullback-Leibler divergence (KLD) scores were calculated to evaluate the distance between a participant's eye gaze distribution and a hypothetical uniform distribution within the RCFT figure. Narrower gaze distributions within the RCFT figure, which yielded higher KLD scores, indicated that the participant was more obsessed with detail and had less organizational strategy. The OCD patients showed lower organizational scores than the HCs. Although no group differences in KLD scores were noted, KLD scores were significantly associated with organization T scores in the OCD group. The current study findings suggest that eye tracking biomarkers of visual memory encoding provide a rapidly determined index of executive functioning, such as organizational strategies, in OCD patients.

The effect of childhood trauma on the severity of obsessive-compulsive symptoms: A systematic review.

BACKGROUND: Childhood trauma is associated with a range of psychiatric disorders, including obsessive-compulsive disorder (OCD). However, our understanding of the different types of childhood trauma and its impact on the different types and severity of obsessive-compulsive symptoms (OCS) is still in its infancy. AIMS: We conducted a systematic review to synthesise the current knowledge on the possible relationships between childhood trauma and obsessive-compulsive symptoms in clinical and non-clinical populations. METHODS: We systematically searched four electronic databases for studies reporting on childhood trauma and OCS severity. Subsequently, we qualitatively synthesised results of eligible studies and effect sizes were also calculated. RESULTS: Twenty-four studies were included in this systematic review. Most studies used OCD samples (k = 16), with a few studies using a sample comprising of a range of psychiatric disorders (k = 6) and some studies using a general community sample (k = 2). Overall, there was support for a significant relationship between childhood trauma and OCS severity (8 out of 16 of the studies using OCD clinical samples, both studies using general population samples, and 5 out of 6 studies used mixed psychiatric samples). CONCLUSIONS: We found evidence of a significant relationship between exposure to childhood trauma and OCS severity across clinical and non-clinical populations. Our results also suggest that a range rather than a single type of childhood trauma was associated with OCD.