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Genetics of obsessive-compulsive disorder - Coggle Diagram
Genetics of obsessive-compulsive disorder
Introduction
OCD- characterized by intrusive obsessions and/or compulsions that are disturbing and time-consuming (American Psychiatric Association)
Obsessions are images, thoughts or urges that are intrusive and unwanted and are associated
with anxiety, distress, disgust and/or a sense of something being not-just-right.
Compulsions are repetitive behaviors or mental rituals,
obsessive fear of being contaminated will lead to high
levels of distress and compulsive or ritualized washing serves the function of temporarily reducing the distress brought on by the obsession
Treatment for OCD- pharmacological, psychotherapeutic, and surgical (DBS) options.
Epidemiology
females are affected at a slightly higher rate than males in adolescence and adulthood, males are more commonly affected in childhood
early-onset OCD has been associated with a stronger genetic component (Nicolini, Arnold, Nestadt, Lanzagorta, & Kennedy, 2009)
The majority of OCD patients exhibit at least one comorbid
disorder
Multiple risk factors may contribute to the development of
OCD, including both genetic and environmental risk factors
Multiple risk factors may contribute to the development of
OCD, including both genetic and environmental risk factors
OCD can increase the risk of developing other psychiatric disorders such as schizophrenia and anorexia nervosa
Genetic epidemiology
Familial clustering of OCD
play a significant role in the liability of OCD and related symptoms, with evidence of shared genetic features among OCD, Tourette syndrome, ADHD, anxiety disorders, and ASDs
OCD consistently clusters within families, with a recurrence risk among first-degree relatives
The familiality of symptom dimension types varies, with hoarding and contamination/cleaning symptoms reported to have the highest familial risk.
Analysis of relatives of individuals with OCD and obsessive-compulsive symptoms indicates a significant genetic contribution and shared risk factors for OCD and sub-diagnostic OCD symptoms.
Heritability from family and twin studies
Twin and family studies, reviewed by Purty et al. and Browne et al., consistently show that OCD and obsessive-compulsive symptoms have a substantial heritability
Childhood-onset samples show heritability estimates ranging from 45-61% for obsessive-compulsive symptoms.
Studies examining sex differences in heritability estimates yield mixed results, with some reporting higher heritability in males while others find no sex differences.
Assortative mating and maternal effects can inflate estimates of heritability, emphasizing the need for caution in interpreting twin study results.
Molecular genetics
Genetic architecture
Single-nucleotide polymorphism (SNP)-based heritability from GWAS studies has also shed light on the genetic architecture of OCD
Rare variants
Rare variants, including cytogenetic abnormalities, copy number variants (CNVs), and single-nucleotide variants, have been implicated in OCD.
Genome-wide scans indicate that while the overall rate of CNV burden does not differ significantly between OCD patients and controls, there is a potential enrichment of genes related to the brain and an increased burden of neurodevelopmental CNVs, particularly for larger CNVs.
Next-generation
sequencing in OCD is still in its infancy
Sex differences
Further research with larger sample sizes is needed to better understand the role of genetics in sex differences observed in OCD.
Genetic relationships with comorbid disorders
OCD frequently co-occurs with various psychiatric disorders, such as anxiety disorders, ASD, Tourette syndrome, anorexia nervosa, and ADHD.
Large-scale cross-disorder studies have identified significant shared genetic risk between OCD and conditions like anorexia nervosa, Tourette syndrome, bipolar disorder, and schizophrenia.
However, while OCD and ASD share some phenotypic similarities, they do not appear to have a significant genetic correlation.
As sample sizes increase, genetic structural equation modeling will be crucial for identifying shared biological mechanisms between disorders and refining diagnostic classifications.
Clinical and therapeutic implications
Genetic studies of OCD aim to uncover specific genetic risk factors and biological mechanisms underlying the disorder, with the goal of improving prevention and treatment strategies.
Pharmacogenetic studies have explored the role of genetic factors in variable treatment responses in OCD patients, focusing on candidate genes such as those involved in pharmacokinetics, serotonin and glutamate signaling, and others
Recent genetic structural equation modeling (gSEM) studies challenge traditional classifications of psychiatric disorders, suggesting that OCD may be more closely related to conditions like anorexia nervosa and Tourette syndrome than previously thought. This highlights the importance of ongoing research in reshaping our understanding of psychiatric nosology and comorbidity.
Conclusions and future directions
OCD is a heritable disorder influenced by both common and rare genetic variants, as well as environmental factors.
Larger meta-analyses are underway to identify robust genetic variants for OCD and understand its genetic architecture and relationships with other mental health disorders.
Alternative phenotyping strategies, such as measuring obsessive-compulsive symptoms more broadly, may enhance our understanding of OCD and its comorbid conditions.
Understanding the biological mechanisms of OCD through genetics and epigenetics may lead to the development of new treatment strategies and personalized interventions.
Exploring associations between genetics and psychological treatment outcomes could contribute to the development of personalized medicine for OCD.