Image Credit: GrAl/Shutterstock.com
The
other day, I posted a few thoughts on the chemistry of mental
disorders. Today, it will be the genetics of some Mental Disorders(
three) and answer the common question of most, Is Mental Disorder
Inherited?
When I was growing up in the Philippines, my parents advise me not to marry in a family with a history of mental illness, because "crazyness" is inherited. At that time I did not believe it. Today it is known that 17 to 28% of mental disorders are genetic-based. However, Mental disorders are not exclusively genetic. They are caused by both genetic and environmental factors. Here's an article ( see link below) on the Genetics of Mental Disorders that I found very informative.
There are hundreds of different types of mental (or psychiatric) disorders as characterized and defined by the DSM and ICD. Many disorders are under specific categories including (but not limited to):
- Anxiety disorders
- Mood disorders
- Psychotic disorders
- Intellectual disabilities
- Developmental disorders
- Personality disorders
- Eating disorders
- Sleep disorders
- Dissociative disorders
- Sexuality-related disorders
- Substance-use disorders
Within these categories, specific disorders include (to name a few examples):
- Major depressive disorder (depression)
- Schizophrenia
- Psychotic disorder
- Sleepwalking
- Primary Insomnia
- Autistic spectrum disorder (ASD)
- Generalized anxiety disorder (GAD)
- Post-traumatic stress disorder (PTSD)
- Obsessive-compulsive disorder (OCD)
- Anorexia nervosa
- Body dysmorphic disorder
- Dyslexia
- Dementia is also included as a mental disorder in the DSM/ICD due to the vast cognitive and personality impairments that occur, in addition to it primarily being a neurological disease
No one psychiatric or mental disorder has a full 100% genetic basis or heritability, and many environmental factors may strongly influence the likelihood of developing a particular disorder or not – despite the presence or absence of genetic elements. Many of these disorders, therefore, have multi-factorial causes – some genetic and some environmental.
In this article, only those disorders with a strong genetic basis will be highlighted. A large proportion of mental disorders do have a high degree of heritability – that is that the risk of having a disorder if another family member has it significantly increases. Independent of that, there may be specific genetic mutations or polymorphisms that may predispose individuals to a higher risk of mental disorder without a family history.
Genetic mutations, polymorphisms or epigenetic changes (that will be discussed below) can alter the development of the brain in a way that changes the typical wiring of the brain. As such, mental disorders can arise at any point in life e.g., from birth – such as ASD, or later in life in combination with environmental triggers - such as bipolar disorder. These predispositions may lower the threshold required for mental disorders to begin in adults compared to “neurotypical” individuals.
Bipolar disorder
One of the most highly genetically inherited psychiatric disorders is bipolar disorder which may affect as much as 1-4% of the population. Bipolar disorder is characterized by periods of depression followed by periods of abnormally elevated mood (mania/hypomania). Whilst environmental factors are known to be important causes of bipolar disorder, it is estimated that around 70-90% of all cases are attributed to genetic factors.
Specific genetic mutations or polymorphisms (SNPs) within CACNA1C, ODZ4, TRANK1, GNG2, ANK3, TPH2, ITPR2, SHANK2, & NCAN have been identified in genetic studies as candidates for increasing the likelihood of developing bipolar disorder. These may either be directly inherited from parents or form de novo during development.
Schizophrenia
Schizophrenia is thought to have up to 70-80% genetic heritability. Like bipolar disorder, having a first-degree relative with the disorder drastically increases the risk of developing schizophrenia later in life – though environmental factors are also incredibly important. However, separating whether this is due to genetic causes or shared environmental conditions is difficult. The cumulative effect of multiple inherited or de novo mutations/polymorphisms in combination with environmental triggers can increase the risk of developing schizophrenia.
For example, copy number variants (CNVs) involved in DiGeorge syndrome (22q11.2) which includes deletions of around 50 genes including COMT and 17q12 microdeletion syndrome are highly associated with an increased risk of developing schizophrenia – but are also prevalently associated comorbidly with ASD and other intellectual disabilities. Other specific genetic mutations implicated in schizophrenia include genetic disruptions to LAMA2, SETD1A, DPYD, TRRAP, TAF13, ARC & VPS39.
Perhaps the most widely known genetic cause of schizophrenia is DISC1 (disrupted in schizophrenia 1), identified in a Scottish family who had schizophrenia and subsequently other families including in America. However, subsequent GWAS studies have not shown any strong associations between DISC1 and schizophrenia, often with mixed results. Whist DISC1 may not be a commonly implicated gene in GWAS studies, it does still show specific mutation level effects in specific families with schizophrenia e.g., 1q43:11q14 translocation.
Autistic spectrum disorder (ASD)
ASD is a neurodevelopmental disorder usually present from birth. Specific genes have been implicated in ASD including MECP2, SHANK1-3, CACN1E/B2, NRXN, SYNGAP1, UBE3A, KCNQ2/3/5, SCNA2 & SYN1/3 to name a few common examples. Many of these genes are related to specific ion channels and synapses thus suggesting abnormal synaptic and neural network development. It is therefore unsurprising that depending on what genes are implicated (and what mutations occur), there is a large degree of clinical and genetic heterogeneity in ASD owing to such a diverse plethora of genetic mutations in ASD.Summary
In summary, mental (psychiatric) disorders such as bipolar disorder, schizophrenia and ASD have strong genetic bases (mutations, polymorphisms and epigenetic changes) that can be directly inherited from an affected parent, or for de novo during development.
Whilst there are several key genes implicated in specific disorders, there are numerous pleiotropic genes that are implicated in all of these disorders rooted in deficits in single genes (e.g., DCC), and calcium channel genes (e.g., CACNA1C).
Thus, many of these disorders arise due to abnormal neuro development which can either cause disorder from birth (ASD) or strongly predispose individuals to developing psychiatric conditions later in life especially in combination with additional environmental factors such as stress.
https://www.news-medical.net/health/The-Genetics-of-Mental-Disorder.aspx
Meanwhile
enjoy this photo of My Recent Pets-No Signs of Crazyness just love and
bonding-Batman & Robin and my 4th of July lunch rich in
omega-3-fatty acids
Grilled Bangus( Teriyaki Station) and Pork Hock Estofado( Shef.com) with rice and pancit. My veggie will be Steamed Peas( too bad my okra are still not bearing fruits).
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