Sukanya Pati

SCHIZOPHRENIA: MYTH VS.TRUTH

“If you talk to God, you are praying; If God talks to you, you have schizophrenia.”

Schizophrenia is a serious disorder which affects how a person thinks, feels and acts. Someone with schizophrenia may have difficulty distinguishing between what is real and what is imaginary; may be unresponsive or withdrawn; and may have difficulty expressing adequate emotions in social situations.

Schizophrenia is a psychotic mental illness of unknown etiology, made up of complex web of myths with the biggest one being: “it can’t be cured”. Contrary to public perception, schizophrenia is not split personality or multiple personality. The vast majority of people with schizophrenia are not violent and do not pose a danger to others. Schizophrenia is not caused by childhood experiences, poor parenting or lack of willpower, nor are the symptoms identical for each person. Many hypothesis have been created with different perspectives for understanding the cause of this disease, some of these include: biological, psychological, socio cultural, and genetic hypothesizes.

Novel researches regarding the genetic makeup of schizophrenia has discovered 108 specific locations in the human genome that increase risk for schizophrenia. Since advent of anti-psychotics in the 1950s, schizophrenia is a known polygenic disorder. However, because of the unfathomable biological mechanisms controlled by these genes, there have been very limited treatment options. Typical (“conventional”) antipsychotics effectively control the “positive” symptoms such as hallucinations, delusions, and confusion of schizophrenia. Atypical (“New Generation”) antipsychotics treat both the positive and negative symptoms of schizophrenia, often with fewer side effects. The new research has shed light on many loci that contain genes controlling neuronal and synaptic function. These new researches not only implicate genetics behind the disease, but also they render the scientists a new understanding of schizophrenia at a molecular and cellular level.

Expression and repression of many genes linked to schizophrenia are controlled by regulatory regions whose vicinity is far from the targeted region. These regulatory regions control the genes during the looping of DNA that occurs  in chromosome formation. Chromosome conformation capture is new technology to identify the locations where loops of DNA come into contact. The mapping revealed new genes linked to schizophrenia including the brain cell receptors activated by acetylcholine. Region of the genome that holds DRD2 gene produces the dopamine receptors. The muscarinic hypothesis of schizophrenia postulates that the ACh system plays a crucial role in the pathology and treatment of schizophrenia. Data from clinical,  postmortem, neuro-imaging, and preclinical and clinical pharmacology studies support this hypothesis

Caveolin is a multifunctional and scaffolding membrane protein, which involves cholesterol trafficking to plasma lipid microdomain. It organizes and targets synaptic parts of the neurotransmitter and neurotrophic receptor signaling pathways. Caveolins are encoded by CAV-1, 2 and 3 genes. Disruption of the CAV1 would likely ruin the neuronal signaling, which leads to symptoms of schizophrenia in predisposed individuals. Interaction between Caveolin-1, a cell membrane protein, and DISC1, gene that regulates the growth of nerve cells and proper nerve signaling. Decreased levels of caveolin diminishes the expression of DISC1 that also manifests symptoms on a molecular level similar to those seen in schizophrenia.

In schizophrenia, excessive oxidation – which involves the same type of chemical reaction that causes metal to corrode into rust, it’s widely thought to cause inflammation and cellular damage. Intensive energy demands on brain cells leads to accumulation of highly reactive oxygen species, such as free radicals and hydrogen peroxide. Magnetic resonance spectroscopy technique uses MRI scanners to non-invasively measure brain concentration of two molecules, NAD+ and NADH that give a readout of how well the brain is able to buffer out excessive oxidants.

As the role of genetics in the development of the disease has become more clear, we have gained new insights into the molecular mechanisms behind schizophrenia. Antipsychotic treatment for schizophrenia has poor efficacy and alters the cognitive abilities of patients, and the development of new treatment methods has been stalled for 60 years. However, with the improved and profound understanding of the disorder, potential molecular targets show a promising future for the treatment of schizophrenia through gene regulations.

BIBLIOGRAPHY:

  1. David Geffen School of Medicine at UCLA. “Scientists find new genetic roots of schizophrenia.” ScienceDaily. ScienceDaily, 19 October 2016. <www.sciencedaily.com/releases/2016/10/161019160035.htm>.
  2. American College of Neuropsychopharmacology. “MRI scans detect ‘brain rust’ in schizophrenia.” ScienceDaily. ScienceDaily, 7 December 2016. <www.sciencedaily.com/releases/2016/12/161207092955.htm>.
  3. American Physiological Society (APS). “Nerve-signaling protein regulates gene associated with Schizophrenia.” ScienceDaily. ScienceDaily, 5 January 2017. <www.sciencedaily.com/releases/2017/01/170105144339.htm>.
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