Genetic Predisposition to Schizophrenia: Understanding the Role of Calcium Channels

Major mental health disorders conventionally share particular genetic malfunctions. Psychiatric disorders have a tendency to show the medical histories of families, and this suggests probable genetic ancestries to these mental health disorders. These types of mental health disorders can range from autism, ADHD, bipolar disorder, major depression, and schizophrenia. There are several common symptoms between these disorders that propose there may also be similarities at a biological level. Schizophrenia is defined as a chronic recurring psychotic illness that usually begins at the age of young adulthood and is lifelong. Since schizophrenia has affected humans for as long as we have been able to diagnose it and even longer, clinicians know an extensive amount about the clinical characteristics, onset, response to interventions, and tissue response of someone with the illness, it is still unknown, whether schizophrenia embodies a single illness or is more of a syndromic diagnosis. (Medoff, 2000).

The risk for schizophrenia can be inherited. Twin studies have shown essential verification of a genetic predisposition, such as the more closely related a person is to an individual with schizophrenia, the greater the risk of also being diagnosed with the illness. The monozygotic twin of someone who has schizophrenia and also shares the same genome has a 40% to 50% higher risk of contracting the same illness. The occurrence within the general population is roughly 1 %. Schizophrenia can occur in all cultures and people around the world, along with similar genetic risks. Studies with a focus on schizophrenia suggest that this illness is a complex multigenetic disorder with many genes associated with the illness. (Medoff, 2000).

Schizophrenia risk factors are most prominently genetic. Scientists are hopeful that studies with new genetic information within the human genome will be able to progress toward discovering a disease mechanism. Brain-imaging techniques have opened up a new world for direct examinations in terms of the structure, neurochemistry, and function of the schizophrenic brain. This has led to the discovery of variations in two genes that are responsible for coding the cellular mechanics that help to control the movement of calcium into neurons. One of these genes is called CACNA1C, which is known as a protein-coding gene. It affects the brain’s chemical structure, which controls the brain’s functions in emotion, thinking, attention, and memory of a person. A defect in this gene has since been linked to several mental illnesses, such as major depressive disorder, bipolar disorder as well as schizophrenia. (Science, 2018).

Impulsive cells can be defined as cells that are able to fire an action potential in a direct response to depolarization. Neurons, as well as muscle cells, are conventionally impulsive, but numerous other cell types also show changes in voltage that are dependent on calcium entry. Voltage-gated calcium channels respond to membrane potential depolarization. This is done by opening, which allows calcium ions to move down their electrochemical gradient. Ca2+ entry provides a boost of calcium ions to drive many processes within the brain, including hormone secretion, neurotransmitter release, calcium-dependent gene transcription, as well as spontaneous pacemaker activity in some neurons, muscles, and secretory cells. (Dahimene, 2015).

The key roles of voltage-gated calcium channels are extremely critical for cellular function within the brain. It is essential that they are implanted into the plasma membrane in a controlled manner. Voltage-gated calcium channels can be found, clustered in an ordered manner, within the specific plasma membrane of muscles, secretory cells, and neurons. These distinguishing biophysical properties are fundamental to the different subtypes of pore-forming calcium channel subunits. These same properties also regulate by auxiliary subunits and other binding proteins to ensure that the functions of voltage-gated calcium channels are tailored to the different roles fulfilled by subcellular locations. (M Nyegaard, 2010).

Voltage-gated calcium channels can be made up of four different subunits; the pore-forming α1subunit, as well as the auxiliary α2δ and β (and in some cases γ) subunits. The α1 subunits mainly determine the kinetics, voltage dependence, single-channel conductance, as well as pharmacology of these voltage-gated calcium channels. However, many of these properties can be modified by the β and α2δ auxiliary subunits. The functional voltage-gated calcium channels can be formed by one of ten different mammalian calcium channel α1 subunit gene products that are encoded by the CACNA1 genes. This gene can be found at “12p13.3 and encodes the alpha-1C subunit of the L-type voltage-dependent calcium channel Cav1.2.” (M Nyegaard, 2010).

The Cav1.2 couples a temporary surge of membrane permeability for calcium-causing cell-membrane depolarization. This leads to an activated intracellular gene transcription. The CACNA1C gene is commonly expressed within the cardiovascular system as well as the entire nervous system, specifically in the hippocampus and thalamus of the brain.14,15. (M Nyegaard, 2010). It is noted that most of the calcium channel genes mixed up within scientific studies of today do not have a primarily presynaptic function. The L-type channel CaV1.2, which is encoded by CACNA1C, is strongly occupied as a risk gene across the full spectrum of schizophrenia and does not have presynaptic fast transmitter release. These channels mainly play a postsynaptic modulatory role due to being located on the cell bodies and on the dendritic spines and shafts of the cells. (Dahimene, 2015).

The diagnosis of schizophrenia predominantly involves the ruling out of other mental health disorders as well as determining that the symptoms being shown are not because of substance abuse, medication, and/or a medical condition. A diagnosis of schizophrenia can consist of: A physical exam, which can be done to rule out other problems that could be causing the shown symptoms as well as to check for any correlated complications. Tests and screenings can be used to rule out conditions with similar symptoms, as well as screen for alcohol and drugs. The acting physician may also have imaging studies done, like an MRI or CT scan. A psychiatric evaluation, done by either a doctor or a lichened psychiatrist, can check the current mental status by observing not only appearance but also demeanor by asking about thoughts, moods, delusions, hallucinations, substance use, and any potential past or present for violence or suicide. This can also include discussions about family and any personal history required at that time. (Staff, 2018).

Schizophrenia entails the lifelong treatment, even after symptoms subside. Though treatment with medications and psychosocial therapy can help manage schizophrenia., hospitalization may be needed in some extreme cases. The treatment may also include a team of people that can help manage a patient’s illness. This team can include a psychologist, social worker, psychiatric nurse, as well as a case manager to help coordinate care. Medications are the basis of any schizophrenia treatment. Antipsychotic medications are the most commonly prescribed for those diagnosed with schizophrenia. They are used to help manage the symptoms caused by the effect of the brain’s neurotransmitter dopamine. The goal of antipsychotic medications is to effectively manage signs and symptoms with the lowest possible dose because the medications are highly potent and can have extreme side effects on other areas of the body. Other medications, such as antidepressants or anti-anxiety drugs, can also help those with schizophrenia. Since these medications do have extreme side effects, most people diagnosed with schizophrenia stop taking them. (Staff, 2018).

Researchers at the Indiana University School of Medicine have created a test that can predict the likelihood of an individual developing schizophrenia. By combining data from several different studies to identify and prioritize a group of genes that are mostly associated with schizophrenia, the test generates a score and can determine whether an individual is at a lower or higher risk of developing the illness. This group of researchers has also developed a model of schizophrenia. The disease’s underlying causes are a mix of genetic differences that affect the development of the brain as well as neuronal connections along with environmental factors. Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine, said: ‘At its core, schizophrenia is a disease of decreased cellular connectivity in the brain, precipitated by environmental stress during brain development, among those with a genetic vulnerability.’ (Rattue, 2012). Once this test is refined, it could help physicians as well as caregivers to identify which young people in families with a history of schizophrenia are more likely to develop schizophrenia. This helps in promoting early intervention as well as treatment. (Rattue, 2012).

Although schizophrenia is not a single isolated illness, genetic testing may still be able to rule in or rule out some of the factors within genes that can lead to schizophrenia. A genetic test for schizophrenia can have amazing benefits. A simple test can help predict one’s level of risk, identify effective treatments, improve the detection of symptoms, create opportunities for prompt diagnosis and early response, as well as reduce the stigma around mental illness altogether. However, there are a few potential drawbacks, such as a misunderstanding of test results, an increase in the mental illness stigma, and discrimination by employers and insurance companies, as well as a negative impact on one’s mood and hope for the future. However, the benefits outweigh the drawbacks.

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