Rare mental disorders
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Rare Mental Disorders: Insights from Recent Research
Higher Incidence of Mental Health Disorders in Rare Disease Patients
Individuals with rare diseases are significantly more likely to experience mental health disorders compared to the general population. This increased incidence is attributed to the multifaceted impacts of rare diseases on an individual's life, which often predispose them to mental health difficulties. The complexity of diagnosing rare diseases can also lead to misdiagnoses of psychosomatic disorders, further complicating the mental health landscape for these patients1.
Prevalence of Affective and Anxiety Disorders in Rare Disease Patients
A systematic review and meta-analysis have revealed high prevalence rates of affective and anxiety disorders among patients with rare chronic diseases. The pooled prevalence estimates for major depressive disorder were 13.1% for current and 39.3% for lifetime occurrences. Similarly, affective disorders had prevalence rates of 21.2% for current and 46.1% for lifetime occurrences, while anxiety disorders showed rates of 39.6% for current and 44.2% for lifetime occurrences. These findings underscore the critical need for supporting patients in adjusting to their diseases to enhance their overall health and well-being2.
Genetic Contributions to Psychiatric Disorders in Rare Genomic Disorders
Rare genomic disorders (RGDs) significantly elevate the risk for neurodevelopmental psychiatric disorders. RGDs are often associated with multiple psychiatric conditions and affect a broad range of developmental and cognitive functions. The phenotypic expression of RGDs is influenced by additional genomic and environmental factors. Emerging evidence suggests that polygenic risk scores can refine predictions of psychiatric illness in individuals with RGDs, although clinical translation remains challenging due to limited genetic testing and lack of guidelines for managing high-risk individuals3.
Role of Rare Variants in Schizophrenia and Major Depressive Disorder
Whole genome sequencing has identified rare inherited variants that contribute to the genetic liability of schizophrenia and major depressive disorder. These variants are highly personalized, with each patient potentially carrying different variants. For instance, in families studied, multiple rare variants were identified in genes implicated in these disorders, suggesting that these variants may interact and lead to psychiatric conditions5.
Common and Rare Genetic Variants in Psychiatric Disorders
The genetic architecture of psychiatric disorders involves both common and rare variants. Genome-wide association studies (GWAS) have detected associations of common single nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs) with psychiatric disorders. However, the dichotomy between common and rare variants is considered unhelpful, as both types contribute to the genetic risk of these disorders. Larger sample sizes are essential to further understand the biology underlying psychiatric disorders6.
Rare Pathogenic Variants and Neurodevelopmental Psychiatric Disorders
Rare pathogenic variants, including single-gene variants and CNVs, play a significant role in neurodevelopmental psychiatric disorders such as autism and schizophrenia. These variants are found in over 1% of individuals in large health care system populations and confer substantial risk for several psychiatric diagnoses. Diagnostic genetic testing for these variants could improve clinical outcomes through early intervention and therapeutic support8.
Clusters of Rare Disorders and Their Relationship to Anxiety and Depression
Research has identified clusters of rare disorders that are associated with varying levels of anxiety and depression. These clusters are based on characteristics such as age of symptom onset, disease course, and symptom severity. The most distressing clusters include those with early onset and severe symptoms, highlighting the need for targeted interventions for individuals in high-risk clusters9.
Conclusion
The relationship between rare diseases and mental health is complex and multifaceted. High prevalence rates of affective and anxiety disorders among rare disease patients, coupled with the significant genetic contributions to psychiatric disorders, underscore the need for comprehensive and sensitive psychiatric care. Advances in genetic research and diagnostic testing hold promise for improving clinical outcomes for individuals with rare mental disorders.
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Most relevant research papers on this topic
“It’s not all in my head!” - The complex relationship between rare diseases and mental health problems
Rare diseases significantly increase the incidence of mental health disorders, and sensitivity and understanding are crucial for effective psychiatric care.
Affective and anxiety disorders in patients with different rare chronic diseases: a systematic review and meta-analysis
High prevalence rates of affective and anxiety disorders exist in adults with various rare chronic diseases, highlighting the need for support in disease adjustment for overall health and well-being.
Meta-Analysis
Rigorous JournalGenes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology.
The Genes to Mental Health Network (G2MH) aims to map the combined effects of rare and common genetic variants on cognitive and psychopathology dimensions, potentially improving patient outcomes.
Genomewide association studies: history, rationale, and prospects for psychiatric disorders.
GWAS have identified associations of common SNPs and rare copy number variants with psychiatric disorders, but more findings are likely and therapeutic applications require further effort.
Systematic Review
Highly CitedWhole Genome Sequencing Revealed Inherited Rare Oligogenic Variants Contributing to Schizophrenia and Major Depressive Disorder in Two Families
Inherited rare oligogenic variants may contribute to the heritability of psychiatric disorders in two families studied through whole genome sequencing.
Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses
The dichotomy between common and rare psychiatric genetic variants is false and unhelpful, and larger experimental sample sizes are essential for understanding the biology underlying these disorders.
Literature ReviewRigorous JournalHighly CitedExome sequencing in families with severe mental illness identifies novel and rare variants in genes implicated in Mendelian neuropsychiatric syndromes
NGS approaches in family-based studies can identify novel and rare variants in genes for complex disorders like severe mental illnesses, with potential pleiotropic effects in the etiology of these illnesses.
Observational StudyRigorous JournalPrevalence and Penetrance of Rare Pathogenic Variants in Neurodevelopmental Psychiatric Genes in a Health Care System Population.
Rare single-gene variants and CNVs are found in over 1% of individuals and play a significant role in mental health disorders like autism, schizophrenia, and bipolar disorder.
Observational StudyRelationship of rare disorder latent clusters to anxiety and depression symptoms.
Rare disorder clusters, such as stable, late onset, moderate, invisible, and very severe, are associated with higher anxiety and depression symptoms.
Observational StudyLarge recurrent microdeletions associated with schizophrenia
Large recurrent microdeletions at 1q21.1, 15q11.2 and 15q13.3 significantly associate with schizophrenia and related psychoses, suggesting that rare, recurrent risk variants may account for a larger fraction of overall genetic risk than previously assumed.
Observational StudyHighly Cited