Mental Disorders And The Genetics

In the absence of genetic factors, many environmental factors can strongly influence the likelihood of developing a particular mental health issue or not – regardless of their presence or absence. In many cases, these disorders are caused by a combination of genetic and environmental factors.

Only disorders with a strong genetic source will be discussed in this article. A large percentage of mental health issues are highly heritable, meaning that your chances of developing one are greatly increased if you have a family history of it. Conversely, in the absence of a family history of mental health issues, individuals may be predisposed to them by certain genetic mutations or polymorphisms.

The normal wiring of the brain can be altered by genetic mutations, polymorphisms, or epigenetic changes (discussed in more detail below). As a result, mental diseases can manifest at any point in life, whether at birth – as in the case of autism spectrum disorder (ASD) – or later in life, when environmental factors are present, as in the case of bipolar disorder. However, when compared to “neurotypical” people, these predispositions may lower the threshold for adult mental disorders to begin.

Mental health issues and genetics: Schizophrenia

According to current research, genetics may account for 70-80% of the risk of schizophrenia. When a person has a first-degree relative, afflicted by the illness, their chances of developing schizophrenia in later years rise dramatically. However, other factors at play are just as important. Distinguishing between genetic and shared environmental factors is difficult, however. Schizophrenia can be exacerbated by a combination of multiple inherited or acquired polymorphisms and environmental stressors.

Co-occurring disorders such as autism spectrum disorders (ASDs) and schizophrenia have been linked to a variety of genetic abnormalities, including copy number variants (CNVs) in the DiGeorge syndrome (22q11.2), which includes deletions of up to 50 genes, including COMT and 17q12 microdeletion syndrome (MDS). DPYD, TRRAP, TAF13, ARC and VPS39 are just some of the other genes whose disruptions have been linked to schizophrenia.

Autism and the genetics

In most cases, autism is a neurodevelopmental disorder that manifests itself before the age of two. Some common examples of genes that have been linked to ASD include MECP2, SHANK1-3, CACN1E/B2, NRXN, SYNGAP1, UBE3A, KCNQ2/3/5, SCNA2, and SYN1/3. In addition, genes linked to specific ion channels and synapses suggest abnormal development of synapses and neural networks. As a result of the wide variety of genetic mutations found in ASD, it is not surprising that the clinical and genetic characteristics of individuals with ASD vary widely depending on the genes involved (and the mutations that result).

Mental health issues and genetics: Bipolar

It’s estimated that 1-4% of the population suffers from bipolar disorder, one of the most highly inherited psychiatric disorders. There are periods of depression, which are followed by periods of abnormally elevated mood, known as manic or hypomanic episodes. Although environmental factors are known to play a role in the development of the bipolar disorder, it is estimated that 70% to 90% of all cases are due to genetic factors.

Genetic studies have identified specific genetic mutations or polymorphisms (SNPs) within CACNA1C, ODZ4, TRANK1, GNG2, ANK3, TPH2, ITPR2, SHANK2, and NCAN as potential risk factors for bipolar disorder. These can either be passed down from generation to generation, or they can be created during development.

Other Common Mutations

Many of the same mutations, polymorphisms, and epigenetic changes seen in ASD are also found in bipolar disorder, schizophrenia, and other mental illnesses (cross-disorder association). Pleiotropic genes can have a broad impact and many effects from a single gene. CACNA1C (or related calcium channel genes such as CACNB2) appears to be highly implicated in all of these illnesses, indicating the shared pathophysiology of aberrant synaptic formation. Various possibilities have been identified through genetic screening investigations; however, one significant example is DCC (SNP rs8084351). DCC’s protein product aids axonal growth during neurodevelopment and is a critical regulator of white matter projections in the developing brain. DCC loss-of-function mutations cause significant neurodevelopmental problems, including the loss of midline commissural pathways and aberrant white matter tract disarray. RBFOX1 is another important pleiotropic gene (SNP rs7193263). RBFOX1 is a gene that controls the development of NMDA receptors and voltage-gated calcium channels in neurons. In mice with RBFOX1 knockouts, neuronal migration and synapse formation are disrupted in the developing brain, and this SNP also affects these processes. NOX4 is another pleiotropic gene implicated with ASD, schizophrenia, and bipolar disorder (SNP rs117956829). NOX4 promotes neural stem cell proliferation and is a key generator of superoxide in the developing and adult brains.

In conclusion, mental (psychiatric) diseases like bipolar disorder, schizophrenia, and autism spectrum disorder (ASD) have substantial genetic roots (mutations, polymorphisms, and epigenetic modifications) that can be inherited directly from an affected parent or developed de novo during development. While certain important genes are implicated in distinct disorders, numerous pleiotropic genes are implicated in all of these disorders that are anchored in single gene deficiencies (e.g., DCC) and calcium channel genes (e.g., CACNA1C). As a result, many of these disorders arise as a result of abnormal neurodevelopment, which can either cause ASD (autism spectrum disorder) or strongly predispose individuals to develop psychiatric conditions later in life, especially when combined with additional environmental factors like stress.

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