A Comprehensive Review on Obsessive-Compulsive Disorder: An Update Download PDF

Obsessive-compulsive disorder (OCD) is a severe and intricate mental illness that profoundly impacts the lives of individuals affected by it. This comprehensive review aims to thoroughly explore all facets of OCD, encompassing its clinical presentations, prevalence as a common mental disorder, its neurological underpinnings, treatment modalities, and broader societal implications. The subsequent overview seeks to advance mental health awareness and foster empathy by integrating diverse perspectives and synthesizing existing research findings. Ongoing research endeavors are delving into the potential therapeutic uses of ketamine, known for its dissociative properties, as well as psychedelic substances in combination with psychotherapeutic interventions, as innovative approaches to treating OCD. Additionally, the utilization of mindfulness-based interventions, particularly mindfulness-based cognitive therapy (MBCT), is actively being investigated, along with the potential effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an adjunct therapy for obsessive-compulsive disorders. The incidence of suicide attempts among individuals diagnosed with OCD varies widely, ranging from 6% to 51.7%, with an average occurrence of 14.2%. In this review, an updated elaboration of all aspects of the disorder has been given.

Introduction

Obsessive-Compulsive Disorder (OCD) profoundly impacts individuals with persistent distressing thoughts and repetitive behaviors. It's a chronic condition affecting diverse backgrounds and imposing a significant societal burden [1]. The onset of fixations frequently triggers a surge in stress and anguish, lightened by ensuing compulsions. Common fixations incorporate fears of defilement, concerns hurting oneself or others, the requirement for symmetry, devout or moralistic stresses, and meddling considerations [2]. OCD involves obsessions (unwanted thoughts) and compulsions (repeated behaviors). Common obsessions include fears of contamination, while common compulsions include cleaning and checking. OCD is categorized under obsessive-compulsive and related disorders in the DSM-5 [3-5] OCD affects 1-3% of the global population across all ages and has a lasting impact on relationships and work. Understanding genetic, neurobiological, and environmental factors is crucial for effective treatment [6]. Neurobiological studies of OCD implicate brain regions like the orbitofrontal cortex, caudate nucleus, and thalamus, elucidating neural circuit complexities. Genetic research underscores hereditary influences on susceptibility. Treatment modalities encompass Selective serotonin reuptake inhibitors (SSRIs) and Cognitive behavioral therapy (CBT), particularly Exposure and response prevention (ERP), showing promising outcomes when combined [7-9]. The present review gives a detailed account on OCD starting from its history to its treatment for the better understanding about the disease by the researchers and medical person.

Brief History

Historical records dating back centuries describe obsessions and compulsions, with accounts found in texts like the Malleus maleficarum from the 15th century. These phenomena were initially interpreted through religious lenses, as evidenced by accounts of exorcisms. However, by the 19th century, figures like Jean-Étienne Dominique Esquirol began to define obsessions and compulsions in psychiatric terms, linking them to conditions like melancholy. By the early 20th century, the understanding of OCD shifted towards psychological explanations [10, 11]. In the nineteenth century, the rise of faculty psychology, phrenology, and mesmerism influenced the understanding of neurosis as a neuropathological disorder, laying the groundwork for modern concepts of OCD. Philosophical, physiological, and political ideas shaped medical approaches to mental illness during this time. In the 1950s, learning theories extended from phobic disorders to OCD symptoms, leading to the development of behavioral therapy. While successful in reducing compulsive rituals, these theories proved insufficient to explain all OCD symptoms. By the 1980s, research focused on the relationship between OCD and neurological conditions such as epilepsy, Tourette's syndrome, and memory problems [12-14].

Prevalence and Demographics

In the US, approximately 2.3% of individuals experience OCD at some point in their lives, with prevalence rates ranging from 1% to 2.3% among children and teenagers under 18. OCD typically begins early, with an average onset age of 19.5 years [4, 15, 16]. Determining the age of onset and duration is critical in evaluating OCD, but definitions of childhood-onset versus adult-onset vary. Childhood-onset OCD may differ from adult-onset cases in characteristics and risk factors, with a higher frequency in males. The incidence of OCD has a bimodal distribution, with peaks in early childhood and early adulthood, exhibiting distinct gender distributions [17-19]. Recent research shows gender differences in OCD symptom onset: females typically experience symptoms after age 10, peaking during adolescence, while around 25% of males experience symptoms before age 10 [20].

Etiology of OCD

A complex interplay of genetic, neurological, cognitive, and environmental factors contributes to the development of OCD. Exploring these domains is crucial to understanding the diverse origins and maintenance of this mental condition

• Genetic Factors significantly contribute to OCD, with studies indicating a hereditary component. Individuals with a family history of OCD have a higher likelihood of developing the disorder themselves, highlighting the importance of genetic variables in OCD vulnerability [21].
• Neurological Factors: Neuroimaging shows brain irregularities in OCD-related areas like the orbitofrontal cortex and caudate nucleus. CSTC circuit dysfunction is significant. OCD involves neurotransmitter dysregulation, especially serotonin, dopamine, and glutamate [22].
• Cognitive Factors: OCD symptoms stem from distorted thought patterns like exaggerated responsibility and catastrophic thinking, driving compulsive rituals [23].
• Environmental Factors: Stressful events, trauma, and adverse childhood experiences can worsen OCD symptoms, interacting with genetic factors [24].
• Immunological Factors: Immune system dysregulation may contribute to OCD, with autoimmune disorders or infections possibly triggering or worsening symptoms [25].
• Prenatal and Perinatal Factors: Complications, infections, or substance exposure during pregnancy or birth are studied for their potential influence on OCD onset [26].
• Epigenetic Factors: Factors during prenatal or birthing phases, like complications or substance exposure, are examined for their role in OCD development [27].

Types of OCD

• Contamination OCD, involves obsessive fears of contamination, leading to compulsive cleaning or avoidance behaviors. Individuals feel dirty or impure even without direct contact with contaminants, experiencing discomfort and anxiety from unpleasant thoughts. They may wash excessively, use neutralizing strategies, or avoid triggering situations to cope with these feelings [28, 29].
• Checking OCD, affecting up to 80% of individuals with OCD, involves repetitive checking of external items like stoves and locks. This behavior aims to prevent harm, reduce uncertainty, or alleviate discomfort from perceived imperfections [4, 30].
• Symmetry and Ordering OCD focuses on a desire for perfection and symmetry, leading to compulsive behaviors like arranging and organizing items. Individuals with this type of OCD often feel a strong need for things to be precisely aligned or symmetrical, resulting in repetitive actions such as touching or tapping objects [31-33].
• Hoarding OCD is characterized by a persistent difficulty in discarding possessions, which leads to the gradual accumulation of items and the creation of cluttered and disorganized living spaces [34]. Compulsive hoarding involves excessive acquisition and difficulty discarding items, leading to clutter and distress. Approximately 15% to 40% of individuals diagnosed with OCD experience compulsions related to hoarding and saving behaviors [35].
• Pure-O OCD, or Purely Obsessional OCD, involves obsessions with mental compulsions rather than outward rituals. It's characterized by intrusive thoughts and internal cognitive processes used to manage them, lacking a distinct classification in the DSM-5 [36, 37].

Pharmacological Interventions

Treatment for obsessive-compulsive disorder (OCD) often involves pharmacological interventions focused on influencing neurotransmitter systems, particularly serotonin modulation. Medications prescribed for OCD aim to address the complex interplay of neurotransmitters, notably serotonin, to reduce symptoms and improve treatment outcomes.

• Selective Serotonin Reuptake Inhibitors (SSRIs), such as fluoxetine (Prozac), fluvoxamine (Luvox), sertraline (Zoloft), paroxetine (Paxil), and escitalopram (Lexapro), are the primary pharmacological treatment for OCD. These medications work by increasing serotonin levels in the brain, which helps alleviate OCD symptoms [38]. 

Sertraline, for example, functions as a selective inhibitor of serotonin reuptake, prolonging serotonin transmission. Its long elimination half-life of approximately 26 hours allows for once-daily dosing, making it convenient for OCD treatment [39].

Sertraline strongly inhibits serotonin uptake, with minimal impact on dopamine and noradrenaline. It reduces serotonin turnover acutely and prevents depletion of central serotonin stores. It down-regulates central β-adrenoceptors and lacks significant affinity for muscarinic and histamine receptors. Sertraline is slowly absorbed orally, peaking 4 to 8 hours post a 100mg dose. It has linear pharmacokinetics within a 50 to 200mg dosage range, with increased bioavailability and peak plasma concentrations in the presence of food. It is extensively distributed in tissues, metabolized in the liver, and has a 26-hour elimination half-life, supporting once-daily dosing [39].

• Tricyclic Antidepressants (TCAs): TCAs, like clomipramine, are effective for OCD due to their potent serotonin reuptake inhibition (Figure 1). However, they're less commonly prescribed than SSRIs due to their side effect profile [40].

Clomipramine is a drug taken orally to treat OCD, and it is primarily metabolized by the liver through CYP2D6. Metabolites such as desmethylclomipramine and hydroxyclomipramine raise serotonin levels outside cells by blocking reuptake, aiding in the effectiveness of treatment. These activities take place past the blood-brain barrier, boosting serotonin functions important for controlling symptoms of OCD.

• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): SNRIs, like venlafaxine and duloxetine, effectively inhibit the reuptake of norepinephrine and serotonin, showing promise in treating OCD symptoms. Controlled trials suggest they can alleviate symptoms, though outcomes vary across studies [41-43].
• Benzodiazepines, such as clonazepam and lorazepam, are sometimes used to alleviate anxiety symptoms in individuals with OCD (Figure 2). They may be considered when there's no history of dependency or tolerance to ensure safe use [44].

Clonazepam, taken orally, is absorbed through the gastrointestinal tract into the bloodstream, then transported to the central nervous system. There, it binds to GABA receptors, enhancing GABA's inhibitory effect. This increases chloride ion influx, hyperpolarizing neurons and suppressing excitability and neurotransmitter release.

• Monoamine Oxidase Inhibitors (MAOIs): MAOIs, such as phenelzine and tranylcypromine, have shown effectiveness in treating OCD, especially when other antidepressants fail. They are considered as alternatives when standard interventions are inadequate for managing OCD symptoms, highlighting their potential usefulness in treating this condition [45].
• Glutamate Modulators: Glutamate Modulators, like N-acetylcysteine (NAC), show promise in alleviating OCD symptoms by modulating glutamate levels in the brain. Early research suggests NAC's effectiveness, but more comprehensive studies are needed to confirm its therapeutic efficacy for OCD [46].
• Cannabinoid Receptor Modulators: Research on cannabinoids, particularly cannabidiol (CBD), for OCD treatment is ongoing. CBD shows promise in reducing symptoms, but more research is needed to confirm its safety and effectiveness [47].

Psychotherapies

• Cognitive-Behavioral Therapy (CBT): Cognitive-Behavioral Therapy (CBT) is a highly effective treatment for OCD, focusing on understanding the connections between thoughts, emotions, and actions. It aims to identify and change harmful cognitive patterns and behaviors associated with OCD symptoms. Cognitive restructuring involves challenging and altering irrational thoughts, while behavioral strategies target maladaptive behaviors like compulsive rituals, using techniques to promote behavioral change [48, 49].
• Exposure and Response Prevention (ERP), a variant of CBT, is highly effective for OCD. It involves exposing individuals to triggers while preventing compulsive responses, promoting therapeutic progress by confronting anxiety triggers, and abstaining from compulsions [23, 50].
• Virtual Reality (VR) is becoming more common in Exposure and Response Prevention (ERP) therapy. It offers a controlled, immersive environment for exposure exercises, known as Virtual Exposure. VR enhances realism and customization, optimizing therapeutic interventions by simulating scenarios that trigger obsessive responses [51, 52].

Emerging Treatments and Research in the Field

Deep Brain Stimulation (DBS) involves surgically implanting electrodes to regulate brain activity for severe, treatment-resistant OCD [53, 54]. Research is exploring the therapeutic potential of ketamine and psychedelics combined with therapy for OCD [55]. Transcranial Magnetic Stimulation (TMS) uses magnetic fields to modulate brain activity, being studied as a treatment for OCD [56, 57]. Pharmacological interventions targeting the glutamatergic system are under investigation for OCD treatment [58]. Mindfulness-Based Interventions like MBCT and MBSR are being studied to enhance OCD treatment by increasing self-awareness and reducing reactivity to obsessive thoughts [59, 60].

Assessment

• Screening: Using validated measures improves the systematic identification and rating of OCD symptoms. Self-report measures are cost-effective, easy to administer, and help reduce potential biases associated with interviews, making them optimal for initial symptom assessment [61].
• Clinical Assessment: OCD is now categorized under 'Obsessive-Compulsive and Related Disorders' in the DSM-5, having been reclassified from an anxiety disorder in the DSM-4. Diagnosis involves meeting criteria outlined in the DSM-5, which include experiencing obsessions or compulsions causing significant distress or impairment in functioning. Symptoms must not be attributed to substances, other medical conditions, or alternative mental disorders [18, 62]. The primary clinician-assessed metric for measuring OCD severity is the Yale-Brown Obsessive - Compulsions Scale (Y-BOCS). This tool includes a checklist of 69 items covering various obsessions and compulsion themes, allowing for comprehensive assessment. The severity scale consists of five questions, with scores ranging from 0 to 4. Scores categorize OCD severity as subclinical (0-7), mild (8-15), moderate (16-23), severe (24-31), or extreme (32-40) [63]. Obsessive-Compulsive Disorder (OCD) affects individuals and their families significantly. Assessments should include evaluating family accommodation for accurate diagnosis. Involving families in assessments helps gather relevant information and improves treatment adherence, ensuring a comprehensive approach to treatment planning [64-66].
• Cognitive Behavioral Assessment of OCD: A thorough evaluation of OCD with Cognitive Behavioral Therapy (CBT) is best done by a specialist in CBT, like a Cognitive Behavioral Therapist or Psychologist with CBT training. Individuals with OCD may feel ashamed, especially with sensitive obsessions. Using a CBT-based formulation can help understand the issue and plan treatment effectively. Salkovskis (1985) introduced a cognitive model for OCD therapy [67, 68].
• Risk Assessment: Risk to self: Historically, OCD has been linked with a lower suicide risk. However, individuals with OCD may still experience suicidal thoughts and attempts, with varying prevalence rates ranging from 6% to 51.7% for attempts and 26.3% to 73.5% for ideation [69, 70].

Risk to others: People with OCD often grapple with intrusive thoughts related to violence or aggression, leading to distress. This may result in inappropriate protective measures. Evaluating risks to others includes considering potential neglect of dependents, both physically and emotionally, as the demands of OCD can overshadow caregiving responsibilities [71, 72].

• Neurocognitive Assessment: Research suggests that individuals with OCD have cognitive-functional differences compared to healthy controls, including cognitive rigidity, poor executive functioning, processing speed, image recall, decision-making, and error monitoring deficits. They also exhibit impaired response inhibition and cognitive flexibility [73-75].
• Immunological Assessment: Research indicates that inflammation and immune alterations are prevalent in individuals with OCD, suggesting the importance of immunological assessments, particularly for patients resistant to standard treatments or experiencing acute symptoms. Streptococcal infections, characterized by antibodies cross-reacting with autoantigens, can contribute to behavioral and motor disorders. A comprehensive immunological evaluation for OCD patients should involve exploring personal and familial inflammation histories, observing inflammation symptoms, and conducting lab tests to measure inflammation levels [76].

Conclusion

Obsessive-Compulsive Disorder (OCD) impacts between 1% and 3% of humanity and has a big impact on people, families, and society. The disorder manifests in diverse ways, from fears of contamination to hoarding behaviors, highlighting its intricate nature. Factors contributing to OCD include genetic predisposition, environmental influences, neurotransmitter imbalances, and cognitive distortions. Furthermore, OCD often co-occurs with conditions like depression, anxiety, and eating disorders, adding complexity to diagnosis and treatment. The societal impact of OCD encompasses reduced productivity, strained relationships, and stigma, which can impede access to support services. Addressing OCD effectively requires comprehensive approaches that promote awareness, education, early intervention, and equitable access to evidence-based treatments, aiming to mitigate its effects and foster a more understanding and supportive environment for those affected. Pharmacological interventions, primarily SSRIs, and psychotherapy, particularly CBT with ERP, offer hope for individuals grappling with OCD. SSRIs aim to restore neurotransmitter balance, while CBT with ERP challenges distorted thinking and helps confront fears without compulsions, enabling individuals to regain control and lead fulfilling lives.

The future of treating obsessive-compulsive disorder (OCD) appears bright as advancements in therapeutic techniques continue to evolve. One such promising modality is Deep Brain Stimulation (DBS), which shows potential in addressing severe cases of OCD that have proven resistant to conventional treatments. Additionally, there is growing interest in psychedelic-assisted therapies, which offer novel approaches to alleviating OCD symptoms by exploring the therapeutic benefits of substances like psilocybin or MDMA under controlled settings. Furthermore, the advent of personalized medicine heralds a new era in OCD treatment, wherein interventions can be customized according to individual needs and genetic predispositions. This tailored approach holds the promise of enhancing treatment efficacy by addressing the specific biological and psychological factors contributing to each patient's condition.

The horizon of obsessive-compulsive disorder (OCD) treatment shines brightly as innovative modalities continues to emerge, offering renewed hope for individuals grappling with this challenging condition. Among these modalities, Deep Brain Stimulation (DBS) stands out as a beacon of promise, particularly for those afflicted with severe cases of OCD that have proven resistant to traditional treatment approaches DBS can bring much-needed relief where previous therapies have failed by carefully regulating neural activity and implanting electrodes in certain brain areas. Apart from DBS, there's an increasing interest in investigating the potential therapeutic advantages of psychedelic-assisted treatments for OCD. These unconventional treatments involve the controlled administration of substances such as psilocybin or MDMA, often in conjunction with psychotherapy sessions conducted within carefully controlled settings. This innovative approach presents a fresh perspective on symptom alleviation, potentially disrupting entrenched patterns of OCD behavior and cognition and opening up new avenues for long-term healing and recovery. Furthermore, the advent of personalized medicine represents a significant leap forward in the realm of OCD treatment. By tailoring treatment strategies to the unique needs and genetic profiles of each patient, personalized medicine offers the potential for more precise and effective interventions.

In essence, the convergence of these innovative modalities—DBS, psychedelic-assisted therapies, and personalized medicine—heralds a new era in OCD treatment. With continued research, exploration, and refinement of these approaches, we stand poised to unlock transformative breakthroughs that have the potential to transform the landscape of OCD treatment, offering new hope and possibilities for individuals living with this challenging condition.

Acknowledgments: None

Conflict of interest: None

Financial support: None

Ethics statement: None

1. Singh A, Anjankar VP, Sapkale B. Obsessive-compulsive disorder (OCD): A comprehensive review of diagnosis, comorbidities, and treatment approaches. Cureus. 2023;15(11):e48960. doi:10.7759/cureus.48960
2. Barrett PM, Healy LJ. An examination of the cognitive processes involved in childhood obsessive-compulsive disorder. Behav Res Ther. 2003;41(3):285-99.
3. Liu W, Zhang H, He Y. Variation in obsessive-compulsive disorder symptoms and treatments: A side effect of COVID-19. Int J Environ Res Public Health. 2021;18(14):7420.
4. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the national comorbidity survey replication. Mol Psychiatry. 2010;15(1):53-63.
5. Fineberg NA, Reghunandanan S, Brown A, Pampaloni I, Pallanti S. The obsessive–compulsive spectrum: A review of 23 years of research. Indian J Psychiatry. 2012;54(2):121-8.
6. Pauls DL. The genetics of obsessive-compulsive disorder: A review. Dialogues Clin Neurosci. 2010;12(2):149-63.
7. Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: The orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32(3):525-49.
8. Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB. American psychiatric association. Practice guidelines for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164(7 Suppl):5-53.
9. McKay D, Sookman D, Neziroglu F, Wilhelm S, Stein DJ, Kyrios M, et al. Efficacy of cognitive-behavioral therapy for obsessive-compulsive disorder. Psychiatry Res. 2015;225(3):236-46. doi:10.1016/j.psychres.2014.11.058
10. Fornaro M, Gabrielli F, Albano C, Fornaro S, Rizzato S, Mattei C, et al. Obsessive-compulsive disorder and related disorders: A comprehensive survey. Ann Gen Psychiatry. 2009;8:13. doi:10.1186/1744-859X-8-13
11. Pitman RK. Pierre Janet on obsessive-compulsive disorder (1903): Review and commentary. Arch Gen Psychiatry. 1987;44(3):226-32. doi:10.1001/archpsyc.1987.01800150032005
12. Isaacs KL, Philbeck JW, Barr WB, Devinsky O, Alper K. Obsessive-compulsive symptoms in patients with temporal lobe epilepsy. Epilepsy Behav. 2004;5(4):569-74.
13. McElroy SL, Phillips KA, Keck PE Jr. Obsessive-compulsive spectrum disorder. J Clin Psychiatry. 1994;55 Suppl:33-51.
14. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry. 2005;62(6):593-602.
15. Errors in Byline, Author Affiliations, and Acknowledgment in: Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(7):768.  doi:10.1001/archpsyc.62.7.768
16. Zohar AH. The epidemiology of obsessive-compulsive disorder in children and adolescents. Child Adolesc Psychiatr Clin N Am. 1999;8(3):445-60.
17. Geller DA, Homayoun S, Johnson G. Developmental considerations in obsessive compulsive disorder: Comparing pediatric and adult-onset cases. Front Psychiatry. 2021;12:678538. doi:10.3389/fpsyt.2021.678538
18. Pampaloni I, Marriott S, Pessina E, Fisher C, Govender A, Mohamed H, et al. The global assessment of OCD. Compr Psychiatry. 2022;118:152342. doi:10.1016/j.comppsych.2022.152342
19. Geller D, Biederman J, Jones J, Park K, Schwartz S, Shapiro S, et al. Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature. J Am Acad Child Adolesc Psychiatry. 1998;37(4):420-7. doi:10.1097/00004583-199804000-00020
20. Hanna GL. Demographic and clinical features of obsessive-compulsive disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry. 1995;34(1):19-27. doi:10.1097/00004583-199501000-00009
21. Mahjani B, Bey K, Boberg J, Burton C. Genetics of obsessive-compulsive disorder. Psychol Med. 2021;51(13):2247-59. doi:10.1017/S0033291721001744
22. Pittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive-compulsive disorder: Neurobiology, pathophysiology, and treatment. Pharmacol Ther. 2011;132(3):314-32. doi:10.1016/j.pharmthera.2011.09.006
23. Abramowitz JS, Taylor S, McKay D. Obsessive-compulsive disorder. Lancet. 2009;374(9688):491-9. doi:10.1016/S0140-6736(09)60240-3
24. Kracker Imthon A, Antônio Caldart C, Do Rosário MC, Fontenelle LF, Constantino Miguel E, Arzeno Ferrão Y. Stressful life events and the clinical expression of obsessive–compulsive disorder (OCD): An exploratory study. J Clin Med. 2020;9(10):3371.
25. Atmaca M, Onalan E, Yildirim H, Koc M. Serum levels of tumor necrosis factor-alpha and interleukin-6 in obsessive-compulsive disorder. Mediators Inflamm. 2010, Article ID 194586. doi:10.1155/2011/194586
26. Mataix-Cols D, Boman M, Monzani B, Rück C, Serlachius E, Långström N, et al. Population-based, multigenerational family clustering study of obsessive-compulsive disorder. JAMA Psychiatry. 2013;70(7):709-17. doi:10.1001/jamapsychiatry.2013.3
27. Eom GH, Kim KB, Kim JH, Kim JY, Kim JR, Kee HJ. Histone methyltransferase SETD3 regulates muscle differentiation. J Biol Chem. 2014;289(2):347-55.
28. Abramowitz JS. Understanding and treating obsessive-compulsive disorder: A cognitive-behavioral approach. Mahwah, NJ: Lawrence Erlbaum Associates Inc; 2006.
29. Jacoby RJ, Blakey SM, Reuman L, Abramowitz JS. Mental contamination obsessions: An examination across the obsessive-compulsive symptom dimensions. J Obs-Compuls Relat Disord. 2018;17:9-15.
30. Strauss AY, Fradkin I, McNally RJ, Linkovski O, Anholt GE, Huppert JD. Why check? A meta-analysis of checking in obsessive-compulsive disorder: Threat vs. distrust of senses. Clin Psychol Rev. 2020;75:101807.
31. Bloch MH, Landeros-Weisenberger A, Rosario MC, Pittenger C, Leckman JF. Meta-analysis of the symptom structure of obsessive-compulsive disorder. Am J Psychiatry. 2008;165(12):1532-42.
32. Lochner C, Hemmings SM, Kinnear CJ, Nel D, Hemmings SM, Seedat S, et al. Cluster analysis of obsessive-compulsive symptomatology: Identifying obsessive-compulsive disorder subtypes. Isr J Psychiatry Relat Sci. 2008;45(3):164-76.
33. Vellozo AP, Fontenelle LF, Torresan RC, Shavitt RG, Ferrão YA, Rosário MC, et al. Symmetry dimension in obsessive-compulsive disorder: Prevalence, severity and clinical correlates. J Clin Med. 2021;10(2):274. doi:10.3390/jcm10020274
34. Thompson C, de la Cruz LF, Mataix-Cols D, Onwumere J. Development of a brief psychoeducational group intervention for carers of people with hoarding disorder: A proof-of-concept study. J Obs-Compuls Relat Disord. 2016;9(4):66-72.
35. Guazzini A, Gursesli MC, Serritella E, Tani M, Duradoni M. Obsessive-compulsive disorder (OCD) types and social media: Are social media important and impactful for OCD people? Eur J Investig Health Psychol Educ. 2022;12(8):1108-20.
36. Pertusa A, Fullana MA, Singh S, Alonso P, Menchón JM, Mataix-Cols D. Compulsive hoarding: OCD symptom, distinct clinical syndrome, or both? Am J Psychiatry. 2008;165(10):1289-98. doi:10.1176/appi.ajp.2008.07111730
37. Seyfer WS. Misunderstood: Phenomenologically informed research of illness experiences of individuals with “Pure O” OCD. UVM College of Arts and Sciences College Honors Theses; 2021. 102.
38. Pallanti S, Quercioli L. Treatment-refractory obsessive-compulsive disorder: Methodological issues, operational definitions and therapeutic lines. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(3):400-12. doi:10.1016/j.pnpbp.2005.11.028
39. Murdoch D, McTavish D. Sertraline: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Drugs. 1992;44(4):604-24. doi:10.2165/00003495-199244040-00007
40. Greist JH, Jefferson JW, Kobak KA, Katzelnick DJ, Serlin RC. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder: A meta-analysis. Arch Gen Psychiatry. 1995;52(1):53-60. doi:10.1001/archpsyc.1995.03950130053006
41. Stein DJ, Costa DLC, Lochner C, Miguel EC, Reddy YCJ, Shavitt RG, et al. Obsessive-compulsive disorder. Nat Rev Dis Primers. 2019;5(1):52. doi:10.1038/s41572-019-0102-3
42. Fineberg NA, Reghunandanan S, Simpson HB, Phillips KA, Richter MA, Matthews K, et al. Obsessive–compulsive disorder (OCD): Practical strategies for pharmacological and somatic treatment in adults. Psychiatry Res. 2015;227(1):114-25.
43. Bandelow B. The medical treatment of obsessive-compulsive disorder and anxiety. CNS Spectr. 2008;13(S14):37-46. doi:10.1017/S1092852900026924
44. Grant JE, Baldwin DS, Chamberlain SR. Time to reconsider monoamine oxidase inhibitors for obsessive compulsive disorder? A case series using phenelzine. J Clin Psychopharmacol. 2021;41(4):461-4. doi:10.1097/JCP.0000000000001418
45. Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: A double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009;66(7):756-63. doi:10.1001/archgenpsychiatry.2009.60
46. Blessing EM, Steenkamp MM, Manzanares J, Marmar CR. Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics. 2015;12(4):825-36. doi:10.1007/s13311-015-0387-1
47. Salkovskis PM. Understanding and treating obsessive-compulsive disorder. Behav Res Ther. 1999;37 Suppl 1:S29-52.
48. Nezgovorova V, Reid J, Fineberg NA, Hollander E. Optimizing first line treatments for adults with OCD. Compr Psychiatry. 2022;115:152305. doi:10.1016/j.comppsych.2022.152305
49. Lack CW. Obsessive-compulsive disorder: Evidence-based treatments and future directions for research. World J Psychiatry. 2012;2(6):86-90. doi:10.5498/wjp. v2.i6.86
50. Anderson PL, Price M, Edwards SM, Obasaju MA, Schmertz SK, Zimand E, et al. Virtual reality exposure therapy for social anxiety disorder: A randomized controlled trial. J Consult Clin Psychol. 2013;81(5):751-60. doi:10.1037/a0033559
51. Opriş D, Pintea S, García-Palacios A, Botella C, Szamosközi Ş, David D. Virtual reality exposure therapy in anxiety disorders: A quantitative meta-analysis. Depress Anxiety. 2012;29(2):85-93. doi:10.1002/da.20910
52. Greenberg BD, Gabriels LA, Malone DA Jr, Rezai AR, Friehs GM, Okun MS, et al. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: Worldwide experience. Mol Psychiatry. 2010;15(1):64-79. doi:10.1038/mp.2008.55
53. Lapidus KA, Stern ER, Berlin HA, Goodman WK. Neuromodulation for obsessive-compulsive disorder. Neurotherapeutics. 2014;11(3):485-95. doi:10.1007/s13311-014-0287-9
54. Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38(12):2475-83. doi:10.1038/npp.2013.150
55. Mantovani A, Lisanby SH, Pieraccini F, Ulivelli M, Castrogiovanni P, Rossi S. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). Int J Neuropsychopharmacol. 2006;9(1):95-100. doi:10.1017/S1461145705005729
56. Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, et al. Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: A prospective multicenter randomized double-blind placebo-controlled trial. Am J Psychiatry. 2019;176(11):931-8. doi:10.1176/appi.ajp.2019.18101180
57. Grant P, Lougee L, Hirschtritt M, Swedo SE. An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2007;17(6):761-7. doi:10.1089/cap.2007.0021
58. Hoge EA, Bui E, Marques L, Metcalf CA, Morris LK, Robinaugh DJ, et al. Randomized controlled trial of mindfulness meditation for generalized anxiety disorder: Effects on anxiety and stress reactivity. J Clin Psychiatry. 2013;74(8):786-92. doi:10.4088/JCP.12m08083
59. Zhang T, Wang L, Bai Y, Zhao W, Wu Y, Jiang W, et al. Mindfulness-based cognitive therapy in major depressive disorder: A study protocol of a randomized control trial and a case-control study with electroencephalogram. Front Psychiatry. 2021;12:499633. doi:10.3389/fpsyt.2021.499633
60. Rapp AM, Bergman RL, Piacentini J, McGuire JF. Evidence-based assessment of obsessive-compulsive disorder. J Cent Nerv Syst Dis. 2016;8:13-29. doi:10.4137/JCNSD.S38359
61. American Psychiatric Association. Diagnostic and statistical manual of mental disorders fourth edition text revision (DSM-IV-TR). Washington DC: American Psychiatric Association; 2000.
62. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, et al. The Yale-brown obsessive compulsive scale: I. development, use, and reliability. Arch Gen Psychiatry. 1989;46(11):1006-11. doi:10.1001/archpsyc.1989.01810110048007
63. Lebowitz ER, Panza KE, Su J, Bloch MH. Family accommodation in obsessive-compulsive disorder. Expert Rev Neurother. 2012;12(2):229-38. doi:10.1586/ern.11.200
64. Lebowitz ER, Panza KE, Bloch MH. Family accommodation in obsessive-compulsive and anxiety disorders: A five-year update. Expert Rev Neurother. 2016;16(1):45-53. doi:10.1586/14737175.2016.1126181
65. Menchón JM, van Ameringen M, Dell'Osso B, Denys D, Figee M, Grant JE, et al. Standards of care for obsessive-compulsive disorder centers. Int J Psychiatry Clin Pract. 2016;20(3):204-8. doi:10.1080/13651501.2016.1197275
66. Weingarden H, Renshaw KD. Shame in the obsessive-compulsive related disorders: A conceptual review. J Affect Disord. 2015;171:74-84. doi:10.1016/j.jad.2014.09.010
67. Salkovskis PM. Obsessional-compulsive problems: A cognitive-behavioral analysis. Behav Res Ther. 1985;23(5):571-83. doi:10.1016/0005-7967(85)90105-6
68. Goodwin DW, Guze SB, Robins E. Follow-up studies in obsessional neurosis. Arch Gen Psychiatry. 1969;20(2):182-7. doi:10.1001/archpsyc.1969.01740140054006
69. Albert U, De Ronchi D, Maina G, Pompili M. Suicide risk in obsessive-compulsive disorder and exploration of risk factors: A systematic review. Curr Neuropharmacol. 2019;17(8):681-96. doi:10.2174/1570159X16666180620155941
70. Veale D. Risk assessment and management in obsessive-compulsive disorder. Adv Psychiatr Treat. 2009;15:332-43. Available from: https://www.academia.edu/29517679/Risk_assessment_and_management_in_obsessive_compulsive_disorder
71. Salkovskis PM, Harrison J. Abnormal and normal obsessions--A replication. Behav Res Ther. 1984;22(5):549-52. doi:10.1016/0005-7967(84)90057-3
72. Fineberg NA, Apergis-Schoute AM, Vaghi MM, Banca P, Gillan CM, Voon V, et al. Mapping compulsivity in the dsm-5 obsessive compulsive and related disorders: cognitive domains, neural circuitry, and treatment. Int J Neuropsychopharmacol. 2018;21(1):42-58. doi:10.1093/ijnp/pyx088
73. Watkins LH, Sahakian BJ, Robertson MM, Veale DM, Rogers RD, Pickard KM, et al. Executive function in Tourette's syndrome and obsessive-compulsive disorder. Psychol Med. 2005;35(4):571-82. doi:10.1017/s0033291704003691
74. Chamberlain SR, Fineberg NA, Menzies LA, Blackwell AD, Bullmore ET, Robbins TW, et al. Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164(2):335-8. doi:10.1176/ajp.2007.164.2.335
75. Sigra S, Hesselmark E, Bejerot S. Treatment of PANDAS and PANS: A systematic review. Neurosci Biobehav Rev. 2018;86:51-65. doi:10.1016/j.neubiorev.2018.01.001
76. Aron AM, Freeman JM, Carter S. The natural history of Sydenham’s chorea review of the literature and long-term evaluation with emphasis on cardiac sequelae. Am J Med. 1965;38(1):83-95. doi:10.1016/0002-9343(65)90162-2