Introduction:
The genetic makeup of schizophrenia is very complex, polygenic (characteristics influenced by two or more genes), and heterogenous (characteristics that occur through different genetic mechanisms). Schizophrenia is a neurological disorder, they are affected by false perception. It affects about one percent of the population and males are commonly affected. The majority of patients have frequent relapses while some suffer lifelong. Patients with schizophrenia have a high risk of misusing drugs. Patients who exhibit features of schizophrenia and other mood disorders such as depression and bipolar disorder are referred to as schizoaffective disorder. There are numerous genetic variants that are involved in the risk of schizophrenia. But, there is limited knowledge about the cause and development of schizophrenia. The genes which are associated with schizophrenia are neuregulin, dysbindin, G72 and d-amino acid oxidase, proline dehydrogenase, catechol-o-methyltransferase, and regulator of G protein signaling. Genetic and environmental factors contribute to an increased risk of developing schizophrenia.
What Is Schizophrenia?
Schizophrenia also called dementia praecox is a neurological disorder, that affects the person’s ability to interpret reality and perceptions. The symptoms become evident during early adulthood. They are affected by hallucinations, delusions which are most common, and other symptoms such as facial ticks, slow movements, or inability to move, which is mostly due to the side effects of medications that are prescribed. Suicidal thoughts and substance abuse are more common in this disorder.
What Are the Clinical Features of Schizophrenia?
Clinical features of schizophrenia include:
- Hallucinations (a false perception of events) can include auditory (most common), vision, touch, and smell senses.
- Delusions (a false belief).
- Decreased functional ability in social gatherings like work or school.
- Erratic behaviors and speech.
- Inability to think and concentrate.
- Inappropriate emotions.
- Difficulty in maintaining personal hygiene and everyday tasks.
- Tremors.
- Facial tics (spasms of facial muscles).
- Bradykinesia (slow movements).
- Akinesia (inability to move voluntarily).
- Limited facial expressions.
- Trouble sleeping.
What Is the Genetics of Schizophrenia?
There are variable numbers of genes that are involved in the risk of developing schizophrenia. In most cases there are changes in multiple genes, each contributing small effects and increasing the risk. Environmental factors such as infections before birth, drug abuse, or stress during childhood can also interact with genetic changes and increase the risk of developing this disorder. The genetic variations can include deletions or duplications, for example, a small deletion in the chromosome 22 region called 22q11 is involved in a very small percentage of causing schizophrenia and is called 22q11.2 deletion syndrome, which is associated with problems in immunity, heart abnormalities, and cleft palate.
The genes which are associated with schizophrenia disorder are:
- Neuregulin (NRG-1) -
- It is a protein-coding gene located on chromosome 8p21-p12.
- It helps in the activation and expression of glutamate and other neurotransmitter receptors, which has a part in neurodevelopment, neuronal migration, and cellular differentiation.
- Dysbindin (DTNPB1) -
- It is a protein-coding gene located on chromosome 6p22.3.
- The protein which is formed binds to the dystrobrevin which is a part of the dystrophin receptor complex involved in muscular dystrophy (a disease that causes progressive loss of muscle and results in weakness) pathogenesis.
- These proteins are found in axons (long projections of the nerve cells that carry the impulses) that are located in the regions that are involved in schizophrenia.
- G72 and D-Amino Acid Oxidase (DAAO) -
- G72 is located on chromosome 13q34 and increases the risk of schizophrenia through glutaminergic transmission by lowering the activity of the N-methyl-D-aspartate (NMDA) receptor, which is a receptor of glutamate and causes hypo functioning of glutamate signal, therefore this gene has a part in the neurodevelopment of schizophrenia.
- NMDA receptor is important in the development of neuronal contacts.
- G72 is associated with bipolar disorder also.
- D-amino acid oxidase is located on chromosome 12q24. DAAO gene polymorphism is associated with schizophrenia.
- G72 and DAAO gene together have epistatic effects (a gene that determines whether the trait will be expressed or not) on developing the risk of schizophrenia.
- Proline Dehydrogenase (PRODH2)-
- It is located on chromosome 22q11.21.
- This is involved in transferring redox potential (the tendency of chemical substances either to reduce or oxidize) across the membrane of mitochondria.
- The genetic defect involves microdeletion of a region in 22q11.21, which has a 20 to 30 percent chance of developing schizophrenia.
- Catechol-O-Methyltransferase (COMT) -
- It is located on chromosome 22q11.21.
- COMT codes for a product that causes the inactivation of catecholamines like dopamine.
- The genetic defect can include similar to PRODH, which is microdeletion. Therefore increasing the risk to develop schizophrenia.
- Regulator of G Protein Signaling (RGS-4) -
- It is located on chromosome 1q21–q22.
- In schizophrenia, there is decreased expression of RGS-4.
Other functional genes and regions that are associated with schizophrenia are:
- Dopamine D3 receptor (DRD3), which is located on chromosome 3q13.3, and the serotonin-2A receptor gene (HTR2A), which is located on chromosome 13q14–q21 is associated with schizophrenia and polymorphism.
- Glutamatergic dysfunction is involved in the pathogenesis of schizophrenia.
- Cholecystokinin (CCK) located on chromosome 3p22–p21.3 is involved in dopaminergic neurotransmission and therefore plays a role in the development of schizophrenia.
- Other chromosomal regions that are involved in schizophrenia are the long arm of chromosomes 1, 2, 5, 6, 8, 10, 13, 15, and 22.
What Is the Treatment for Schizophrenia?
There is no definitive cure for this disorder. It mainly involves:
- The use of antipsychotic medications relieves psychotic symptoms such as hallucinations, delusion, and confused thinking.
- Psychological treatments such as supportive psychotherapy and cognitive behavioral therapy help in reducing stress and improving social skills.
- Psychosocial supports help in learning social skills, relieving stress, helps in identifying the signs of relapse, and periods of remission.
- Support from family is very important that can improve patients' health and well-being.
Conclusion:
With the help of a haplotype structure map (HapMap), it is possible to find genes that are associated with schizophrenia and their functional significance of variations. The HapMap contains patterns of DNA sequence, sequence variations, frequencies, and interrelationships between them. These can help in understanding the disease, and its response to drugs.
