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Genetics of obsessive-compulsive disorder - Coggle Diagram
Genetics of obsessive-compulsive disorder
Introduction
Intrusive obsessions (unwanted thoughts, images, urges) causing anxiety, distress, etc.
Common obsessions: harming others, being bad, contamination fears.
Repetitive compulsions (behaviors/mental rituals) to reduce anxiety or prevent feared events.
OCD exists on a spectrum, with varying degrees of obsessiveness and compulsion present in everyone.
Individuals with OCD experience these symptoms at an extreme
First described of OCD in 1838 by Jean-Étienne Esquirol.
OCD recently reclassified as a an anxiety disorder.
Symptoms (obsessions, compulsions) vary greatly between individuals.
Selective serotonin reuptake inhibitors (SSRIs) + cognitive behavioral therapy (CBT) including exposure and response prevention (ERP) provide relief from OCD symptoms.
Pharmacological options are clomipramine or atypical antipsychotics (risperidone, aripiprazole)
Efforts needed to identify OCD earlier for faster intervention.
Understanding the root causes of OCD is crucial for better prevention and treatment.
Epidemiology
Females slightly more affected.
Males are more commonly affected in childhood
Bimodal distribution with peaks in adolescence (13-18 years) and early adulthood
Suggests childhood-onset OCD might be a distinct subtype which is specific clinical features and potentially different etiological factors.
Other common overlaps include autism, eating disorders, and ADHD.
Most OCD patients have another mental health condition, especially depression, anxiety, and personality disorders.
OCD can also occur with Tourette syndrome, neurological conditions, and brain injuries.
OCD can severely impact daily life, particularly social relationships.
Compared to the general population, OCD patients have a higher risk of death by natural or unnatural causes
Research shows a substantial percentage of OCD patients experience suicidal thoughts and attempts (average lifetime rate of 14.2%).
Multiple contributing factors of OCD such as genetics, environment (like birth complications, trauma, life events), and even inflammation play a role.
OCD can raise the risk of developing conditions like schizophrenia or anorexia, and vice versa.
The striatum supports the compulsive actions often seen in OCD.
Genetic epidemiology
Familial clustering of OCD
Around 1-3% of people experience OCD in their lifetime.
Recurrence patterns align with an additive genetic model.
OCD tends to cluster in families, suggesting a genetic link.
Relatives of individuals with OCD show increased risk, suggesting shared genetic factors.
Hoarding and contamination/cleaning behaviors have the strongest family link.
OCD shares genetic links with Tourette syndrome, anxiety disorders, and ASDs.
Symmetry-related symptoms might be more common in familial OCD than cases without a family history.
Tourette syndrome has even stronger familial clustering than OCD.
These disorders often co-occur in individuals and families.
Heritability from family and twin studies
Identical twins (MZ) share much higher OCD risk than non-identical twins (DZ).
Childhood studies estimate 45-61% heritability for OCD symptoms.
Each OCD symptom has a genetic component, but some, like hoarding, may have additional unique genetic factors.
Molecular genetics
Common variants
Focused on specific genes linked to brain chemicals relevant to OCD.
These approaches are identifying significant genes associated with OCD, like PTPRD.
The Psychiatric Genomics Consortium is analyzing data from thousands of OCD patients and controls.
Genetic markers may vary based on specific OCD symptoms, with a stronger link to compulsive symptoms.
Studies also investigate genetic links to OCD symptoms and traits in general populations.
Genetic architecture
Reveal the genetic makeup of OCD through single-nucleotide polymorphisms (SNPs).
Compulsive symptoms show stronger genetic links and heritability than obsessive symptoms.
Genetic contribution from rare variants (MAF 0.1%-5%) appears reported to be 0%, but findings need further confirmation.
Rare variants
Older studies identified cytogenetic abnormalities in some OCD patients.
High-resolution studies suggest specific rare genetic variations (copy number variants and single-nucleotide variants) play a role.
No significant difference found between OCD patients and controls, but larger CNVs might impact brain-related genes and increase risk for neurodevelopmental conditions.
Larger studies are crucial to fully understand the contribution of rare variants to OCD development.
Epigenetics and gene expression
Large-scale studies exploring epigenetics (changes beyond DNA sequence) in OCD are scarce, mainly focusing on DNA methylation.
One study found different gene expression patterns (mRNA) in blood samples from OCD patients compared to healthy controls, with the most prominent change related to ribosomal.
Another study linked genetic variations associated with OCD to gene expression in specific brain regions like the ACC and amygdala.
Larger studies are needed to provide deeper insights into gene expression and its role in OCD.
Genetic relationships with comorbid disorders
OCD frequently overlaps with other mental health issues like anxiety, autism, Tourette's, eating disorders, and ADHD.
Genetics appear to play a role in these connections, especially between OCD and anorexia nervosa.
Recent research using sophisticated methods (gSEM) consistently groups OCD with anorexia, but the broader "cluster" varies depending on the included disorders.
As studies use larger samples and advanced techniques like gSEM, we gain valuable insights into shared biological mechanisms behind different disorders, which can inform future classification systems.
Sex differences
Differences in OCD onset and symptoms between men and women might be linked to genetics.
Only one study so far explored sex differences in OCD's genetic architecture, using data from large research collaborations.
More research with larger samples is crucial to fully understand the role of genetics in these sex-based differences.
Clinical and therapeutic implications
Find genetic risk factors and biological underpinnings for prevention, treatment, and personalized medicine.
Identify more reliable genetic risk factors.
Polygenic risk scores (PRS): Predict risk and treatment response.
Explore genetic influences on treatment effectiveness.
Using advanced genetic analysis (gSEM), researchers are re-evaluating the categorization of mental health conditions like OCD.
While these studies present fascinating insights, the sample sizes are still too small to definitively change classifications.
With larger studies, this approach could revolutionize how we categorize disorders, understand their connections, and develop targeted treatment strategies.
Conclusions and future directions
Evidence shows a large genetic contribution to OCD & its symptoms.
No confirmed genetic markers yet, likely due to smaller study sizes.
Current analyses like genetic correlations & polygenic risk scores might be unreliable due to small samples.
Larger studies by the PGC show promise for identifying key genetic variants and understanding OCD's genetic architecture
Studies need larger samples to confirm initial findings and discover more genetic factors.
Measuring a broader range of obsessive-compulsive symptoms beyond diagnosed cases holds potential for better understanding.
This approach could not only improve understanding of OCD but also related conditions with similar symptoms.
Focusing on specific OCD symptom types to pinpoint their unique genetic contributors.