Neuropsychology

What Causes Schizophrenia?

It has been commonly observed that Schizophrenia runs in families. Besides being genetically inherited, this disorder is also found to be triggered by some traumatic experiences during early adult life. It is now also known that prenatal exposure to infections increases the risk for developing schizophrenia later in life. Besides, childhood experiences of abuse or trauma are also serious risk factors for developing Schizophrenia. Un-Supportive parenting where children develop strained relationships with parents also contribute to an increased risk of this disorder. Thus, early environment plays a crucial role in the surfacing of abrupt behavioral changes in the affected persons.

Certainly, there occurs discrete biochemical changes in the brain cells/neutrons of the victims that result in altered neuro-chemistry which is the hallmark of disintegrated thought process. The network of neurons that is spread all over the human body basically comprises billions of interconnecting neurons that pass on the neural message from one cell to the other in form of specific neuro-chemical signals , which are nothing but biochemical molecules called the ‘neurotransmitters’.

These substances allow brain cells to communicate with each other, and are released in very precise amounts at the junctional points where the dendrites of one neuron intersect with the axon terminals of another neuron. One such neurotransmitter is called ‘dopamine’, which plays a crucial role in brain chemistry. It is the excessive production of dopamine that awe fully disturbs the flow of information through the neural wiring, and thus plays havoc in the thought process, typical of Schizophrenia.

Many different genes seem to be involved in the abnormally raised activity of dopamine in the neurons. Certain genes linked to an increased risk of Schizophrenia have been found, which produce defective proteins that play a crucial role in altering the neural signaling. Rare deletions or duplications of tiny DNA sequences in these genes make them alter their expression, thus causing the production of a defective variant of the normal protein.

It is understood today that there is an increased production of Dopamine Receptor D2, also known as D2R, which is a protein encoded by the DRD2 gene. This is known to give rise to the positive symptoms of Schizophrenia. Therefore, most anti-psychotic drugs cause the D2 blockage or have dopamine blocking effect. However, newer anti-psychotic drugs also affect the production of another neurotransmitter called serotonin.

Indian scientists have made a mark in unraveling the genetic basis of schizophrenia, thanks to the efforts of Dr Samir K. Brahmachari, Director General CSIR and his team comprising scientists at the Institute of Genomics & Integrative Biology (IGIB), New Delhi who in 2003 identified a mutation in a gene named ‘Synaptogyrin 1’ (SYNGR 1 gene), sitting on chromosome 22, which subtly alters the neural signaling pathway and increases individual susceptibility to schizophrenia and bipolar disorder in the Indian populations.

The SYNGR 1 gene has been found to be associated with presynaptic vesicles in neurons and plays a crucial role in transmitting of neural messages. Based on this novel finding, a US patent on ‘Novel Primers for Screening Schizophrenia and a Method Thereof’ was granted in 2004. Similarly, another gene called ‘MLCI’ has also been associated with these mental disorders, which also suggests the likely involvement of a common pathway in the etiology of these disorders.

Glutamate is yet another neurotransmitter. Studies have shown that there is a reduced function of the glutamate receptor in schizophrenics. Abnormally low levels of glutamate receptors are fond in postmortem brains of the victims of this disorder. Substantiating this, it has been found that glutamate blocking drugs can mimic the symptoms with Schizophrenia.

Persons at high-risk of developing this disorder include those having a family history of Schizophrenia and are undergoing some psychotic experience. Psychological treatments and medication seem to be effective in reducing the chances of such ‘high-risk’ people to develop full-blown Schizophrenia.

Traumatic Treatment

First introduced in the 1930s, Electro Convulsive Therapy (ECT), also called electroshock treatment has been a common psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. This treatment is, however, rarely used as a first-line treatment for Schizophrenia and is only considered after long, unsuccessful treatment with anti-psychotic drugs.

Another shock therapy commonly used in the hospital during the 1940s and 1950s was ‘insulin coma therapy’. This psychiatric treatment involved the injection of large doses of insulin that induced symptoms of reduced blood sugar (pallor, perspiration salivation, restlessness) and resulted in coma if the dose of insulin was high. Horrifyingly, patients were subjected to several comas with reducing dose of insulin, before the treatment was stopped. It is no longer practiced now.

Psycho-surgery or neurosurgery for mental disorders was first introduced in 1930s. It basically involved the operation, under general anesthesia where a small piece of brain tissue was destroyed or removed by thermo-coagulation, freezing, cutting or using radiation. Another neurosurgical method to treat schizophrenia has been ‘deep brain stimulation’, where specific areas of the brain are stimulated with implanted electrodes. Although patients do show improvement in their symptoms after neurosurgical treatments, these methods are not a recommended treatment.

Special class of drugs called as anti-psychotic drug help in the treatment of Schizophrenia, as they work by suppressing dopamine activity inside the neurons. It was in 1950 that the drug chlorpromazine—the first drug developed with anti-psychotic action –was synthesized. This drug indeed brought a revolutionary advanced in the treatment of Schizophrenia, as hospitalization could be avoided and social rehabilitation of such persons could be done to a great extent. Chlorpromazine – a ‘benchmark’ drug in the treatment of Schizophrenia –works on several receptors on neurons, blocking the activity of neurotransmitter that act by binding to those receptors. The side effects of this drug include sedation, constipation, hypotension and restlessless. Long term or high dose use of the drug can cause involuntary, repetitive body movements or tremors called ‘tardive dyskinesia’, a condition that is reversible. Similarly another drug group, which blocks dopamine function is called ‘phenothiazines’, which can reduced psychotic symptoms.

Today, however, there are more effective anti-psychotic drugs available. Clozapine is the first of a typical anti-psychotic drug used in the treatment of schizophrenia that was first introduced in Europe in 1971. Although a highly effective drug to treat Schizophrenia, it unfortunately causes a drastic reduction in the number of white blood cells, a condition called agranulocytosis, which can prove fatal. In 1989, the US FDA approved the use of clozapine for only treatment-resistant Schizophrenia, or patients not responding to other anti-psychotic treatments. However, periodic blood testing for patients taking clozapine was made essential to monitor the adverse effects of this drug on the patient.

Risperidone, first released in 1994, is also a common atypical anti-psychotic drug used to treat Schizophrenia. However it induces weight gain and sexual dysfunction besides having the other side effects common to most anti-psychotic drugs. Similarly, another atypical anti-psychotic drug, olanzapine is also associated with considerable weight gain and risk of metabolic syndrome.

Studies have shown that a vast majority of schizophrenics use drugs, alcohol or tobacco, which is suggestive of the victim trying to cope with unpleasant states like depression, anxiety, boredom and loneliness. Substance abuse can make treatment for schizophrenia less effective. In fact, research has found increasing evidence of a link between marijuana and Schizophrenia symptoms. Similarly, smoking tends to make anti-psychotic drugs less effective.

Above all, vocational and social rehabilitation are very important for making schizophrenics lead a less traumatic life. Public education campaigns also assume great importance for reducing the burden of this disorder on human populations, as information about risk factors and early symptoms of this mental disorder can help in timely treatment and social rehabilitation of the affected persons.

Psychotherapy is personal counseling of the patients, aimed at increasing the sense of their own well being. This involves several relationship-building techniques like friendly communication and dialogue for bringing about a behavioural therapy and cognitive remediation help to treat psychotic symptoms, and improve social rehabilitation of schizophrenics.

Positive Approach

The World Health Organization (WHO) coordinated the International Study of Schizophrenia (ISOS) – a long term follow-up study of 1633 individuals diagnosed with schizophrenia around the world-and published the findings in 2001. The results shook the prevalent belief that schizophrenia is a chronic mental illness. Of the 75 per cent who were available for follow-up, half had a favorable outcome, and 16 per cent had a delayed recovery.

It clearly came out that early social intervention was essential for improving patient condition. WHO studies have also shown that individuals diagnosed with schizophrenia have much better long-term treatment outcome in developing countries including (India, Colombia and Nigeria)than in developed countries that include USA, UK, Japan and Russia . Scientists have learnt a lot about schizophrenia, but more research is needed to provide answers to many still unexplained facts. For this, more funding is needed to promote mental health research.

A Rare Accomplishment

It is quite astonishing that a person diagnosed as schizophrenic during college years has the interest to continue his studies, so much so that in later life he is admired for his rare talents in the field of mathematics and is awarded the Nobel Prize for his unique contributions to the field. This man was none other than John Nash, a well acclaimed Us mathematician, a victim of schizophrenia, who won the 1994 Nobel Prize in Economics. His life has even been depicted in a film, A Beautiful Mind.

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