In this article, we will Describe the Negative Symptoms of Schizophrenia. Elucidate the Biological Causes of Schizophrenia.
The Biological Causes of Schizophrenia – Genetic Influences, Prenatal Exposure, Neurodevelopmental Factors, Neuroanatomical Factors, Neurochemical Factors, Neurocognitive Factors are described below:
1. Genetic Influences
Several research studies come from various sources, family studies, twin studies, adopted children studies, linkage and association studies. It has made it clear that genes are important in making a person vulnerable to Schizophrenia. Heritability estimates are stable at 80%. Overall, studies suggest that Schizophrenia is polygenic. There is no one gene responsible for Schizophrenia but multiple combinations of genes that produce vulnerability for Schizophrenia.
Family Studies:
Studies have examined families who have members with Schizophrenia. It found that the severity of a parent’s disorder influences the likelihood of a child developing Schizophrenia. Further, it’s been found that all types of Schizophrenia are often seen during a family. One inherits a general predisposition for Schizophrenia spectrum and psychotic disorders. The Rate of Schizophrenia is highest in monozygotic twins that are 48% compared to the general population, where the prevalence rate is 1%.
Twin Studies:
Studies of Twins with Schizophrenia conclude that if one of the identical twins has Schizophrenia, then 48% of the time the other twin also has Schizophrenia. However, in non-identical twins, the rate is 17%. These studies show that genes play an important role in causing Schizophrenia. If only genes played a role then the consistency rate of identical twins should have been 100% since they share genetic material. Whereas, if the environment only played a role then the consistency rate should have been 0%. Another study examines the rates of Schizophrenia in offsprings of discordant twins (one sibling has Schizophrenia and the other didn’t) and found the rate the same (17%). It suggests that perhaps the well-twin is that the carrier of Schizophrenia genes which was never expressed but passed on to others.
The classic Case Study of Genain Quadruplets illustrates the role of genetic influences in Schizophrenia. All four sisters were diagnosed with some kind of Schizophrenia. However, it found that the time of onset for Schizophrenia, symptoms, type of Schizophrenia, course of the disorder, and ultimately the outcomes differed significantly from one sister to another. This is because all identical twins don’t have similar prenatal environments. Around two-thirds of identical twins’ embryos are monochorionic, which means they share a placenta and blood supply. The remaining identical twins and all non-identical twins are dichorionic; they have separate placentas and separate fetal circulations. Studies have found that identical twins who are monochorionic are much more likely to be concordant for Schizophrenia (around 60%) than monozygotic twins who are dichorionic (around 11%).
Adoption Studies:
It is one reason that monozygotic twins (identical twins) could have a higher rate for Schizophrenia because they are more likely to be raised in more similar environments than dizygotic (non-identical twins). This is because identical twins are always of the same gender. Thus, it is reasonable to assume that twin studies may overemphasize the importance of genetics in the causality of schizophrenia. Adoption studies can help in truly distinctive between the roles of the environment and genetics. Adoption studies suggest that the concordance rate is higher between biological relatives and not adoptive relations of people who go on to develop Schizophrenia.
Heston followed children born to mothers in a state mental hospital suffering from Schizophrenia. About 16.6% developed Schizophrenia, whereas none of the 50 control children (born to mothers without Schizophrenia, but given up for adoption) developed Schizophrenia. Twin and adoption studies are taken together to connect the role of genetics in the aetiology of Schizophrenia. However, the environment in which children are raised also plays a role. For example, researchers found lower concordance rates between biological mothers with Schizophrenia. Their children were raised in supportive homes compared to those who grew up in non-supportive households. These findings are positive because they suggest that a supportive environment can become protective for people with genetic vulnerability for Schizophrenia.
Molecular Genetics:
Research suggests that the genetic makeup of an individual makes her/him vulnerable to Schizophrenia spectrum disorders and not just Schizophrenia in particular. It is also important to understand that there is no ‘one gene’ for Schizophrenia. Preferably, several genes working in combination lead to vulnerability to the Schizophrenia spectrum and other psychotic disorders. Through linkage analysis, a method for resulting out if Schizophrenia occurs with a known DNA marker trait-like blood group and colour-blindness. Researchers were able to find chromosomes: 1, 2, 3, 5, 6, 8, 10, 11, 13, 20, and 22 for their role in Schizophrenia. Recent studies have been able to identify candidate genes on the chromosomes. For example, the COMT gene (Catecholamine O-methyl Transferase) on chromosome 22 is in particular important, because it has involved in dopamine metabolism.
2. Prenatal Exposure
Whether or not a genotype indicates or not depends on biological and environmental triggers. Genes triggered ‘on’ and ‘off’ because of prenatal exposures. Research suggests that in identical twins who are discordant for Schizophrenia some environmental factors hit ‘on’ for genes of Schizophrenia for the twin that goes on to develop Schizophrenia and not for the healthy twin. Consistent with the diathesis-stress model, prenatal exposures to infections and other stressors in people with genetic vulnerability for Schizophrenia may precipitate to cause Schizophrenia in adulthood. Thus, a genetic predisposition for Schizophrenia may predispose an individual to suffer more environmental damage than would be the case with a child without any genetic predisposition.
Viral Infections:
Viral infections have been suggested to play a key role in the development of Schizophrenia. In the northern hemisphere, more people are born between January and March with schizophrenia. It would be predicted that the role of a seasonal infection. Risk of Schizophrenia increases if the mother gets the flu in the fourth to seventh month of pregnancy. Other maternal infections like toxoplasmosis (a parasitic infection) and rubella have also been linked to the increased possibility of developing Schizophrenia. It has been hypothesized that the antibodies developed in the mother’s body against the infection may cross the placenta and disrupt the neurodevelopment of the fetus.
Rhesus Incompatibility:
Rhesus (Rh) incompatibility occurs when an Rh-negative mother carries an Rh-positive fetus. Studies have found that the rate of schizophrenia is about 2.1% in males who are Rh-incompatible with their mothers. For males who have no such incompatibility with their mothers, the rate of schizophrenia is 0.8% – which is near the expected frequency rate for the general population. Rh incompatibility has been connected to birth complications. It may lead to brain abnormalities of the type associated with Schizophrenia.
Pregnancy and Birth Complications:
The probability of patients with Schizophrenia with a history of a complicated pregnancy or birth complication (e.g., prolonged labour, breech delivery, or the umbilical cord around the baby’s neck) is high. Although there is much to learn, but these findings do recommend that damage to the brain at the critical time of development is an important precursor to schizophrenia.
Early Nutritional Deficiency and Maternal Stress:
It was found that children conceived at the height of famine had a two-fold increase in the development of Schizophrenia later. General malnourishment is connected to abnormal brain development. Similarly, maternal stress experienced in the first trimester of pregnancy and early in the second trimester has also been connected to an increased risk of Schizophrenia.
3. Neurodevelopmental Factors
According to some researches, Schizophrenia may be a neurodevelopmental disorder that stems from brain lesions. It occurs very early in development, possibly even before birth. The brain lesions lie dormant till normal maturation shows issues in adult age. If this is the case then we should be able to see early indications of the condition before the illness sets in. Retrospective studies or trying to study the childhood of people diagnosed with Schizophrenia in the present provide some evidence for this. The researcher showed home videos of the childhood of people diagnosed with schizophrenia and found less positive facial emotions, more negative facial emotions and unusual hand movements. Likewise, prospective studies identified high-risk children or those high on genetic vulnerability to develop Schizophrenia. It found that these children were poorer than control children on measures of attention as well were rated lower on social competence.
4. Neuroanatomical Factors
Brain Volume:
Since Schizophrenia has a strong biological aetiology, it has been recommended that possibly the brain of people with Schizophrenia may be anatomically different than typical others. However, brain scans can’t be used for diagnosis. Neuroanatomical differences have been reported in the brains of people with Schizophrenia relative to control groups. Though it may not be found in everyone with Schizophrenia, but a large number of studies have shown that compared with controls, people with schizophrenia have enlarged brain ventricles. This finding has been testified as early as 1927 when post-mortem brains of people with Schizophrenia showed enlargement. This enlargement of ventricles means that either the surrounding brain areas have shrunken or have not developed fully.
Studies have reported at least a 3% reduction in brain volume relative to controls. Reduction in brain volume has been found in people with recent onset of Schizophrenia and not only those who have had chronic psychosis. This shows that those brain abnormalities may predate the illness rather than develop as a result of untreated psychosis. It’s important to note that reductions in brain volume aren’t progressively degenerative though some studies may show a reduction in grey areas in the brain over time.
Specific Brain Areas:
Researches have suggested that structural issues in brain areas like the amygdala, hippocampus, temporal lobes, and thalamus are present before the onset of Schizophrenia, possibly beginning of the prenatal stage. Additionally, abnormally low activity in the frontal lobe (in particular the pre-frontal lobe) is shown in people with Schizophrenia. Issues in the frontal lobes have been implicated in the negative symptoms and attentional-cognitive deficits found in individuals with Schizophrenia. There is a low density of neurons in the prefrontal cortex of the frontal lobes.
Research has found that people with Schizophrenia have missing “inhibitory interneurons” which regulate the excitability of other neurons. Thus, the brains of people with Schizophrenia are unable to regulate activity in certain brain areas making them incapable of handling even normal levels of stress. The low density of neurons in different areas of the brain may be related to the abnormal synaptic pruning in adolescence/early adulthood of people with genetic vulnerability for schizophrenia. Overall, brain dysfunction in Schizophrenia is clear, but it may manifest differently at different stages of illnesses and different people.
5. Neurochemical Factors
Dopamine Hypothesis:
Schizophrenia is a result of excessive dopamine in the brain. Several observations have led to the dopamine hypothesis.
- Chlorpromazine, a drug used to treat Schizophrenia linked to its ability to block dopamine receptors.
- Antipsychotic drugs such as chlorpromazine can produce negative side effects similar to Parkinson’s disorder (a disorder caused by deficient dopamine).
- Dopamine Agonist (L-dopa) used to treat disorders such as Parkinson’s disease gives rise to psychotic states similar to Schizophrenia.
- Abuse of Amphetamines increases dopamine in the brain and leads to a form of psychosis. For people who abuse the drug, auditory hallucinations and paranoia can be seen and it can worsen symptoms in people with Schizophrenia.
Overall studies have found that dopamine antagonists decrease symptoms of Schizophrenia and dopamine agonists increase symptoms of Schizophrenia. Proof suggests that people with Schizophrenia aren’t producing excessive dopamine, but have an increased number of dopamine receptors. Post-mortem of people with Schizophrenia has been found to show that there are more D2 receptors in brains. The relationship between Schizophrenia and dopamine and isn’t that direct. A significant number of people with Schizophrenia haven’t been helped by antipsychotic medicines that block dopamine receptors. Additionally, antipsychotic medications aren’t very effective for negative symptoms making one question if the dopamine hypothesis accounts for only positive symptoms. Thus, dopamine is involved in symptoms of schizophrenia but the relationship is more complicated than previously conceived.
Glutamate Hypothesis:
Glutamate is an excitatory neurotransmitter and its receptors are called NMDA receptors. NMDA, Ketamine and PCP antagonists are recreational drugs that result in psychotic symptoms. It has been hypothesized that they work by either leading to deficits in glutamate or blocking NMDA receptors. Deficits of glutamate are also found in the post-mortem brains of patients with Schizophrenia. Thus, currently, new drugs for Schizophrenia have been designed to activate glutamate receptors. The dopamine receptors have been found to inhibit the release of glutamate. Overall, it has been proposed that an overactive dopaminergic system can lead to deficits in glutamate leading to under activity of NMDA rectors.
6. Neurocognitive Factors
People with Schizophrenia perform poorer than control individuals on a number of neuropsychological tasks. They have been found to have slower response time, poor sustained attention, and poor working memory. For example, performance is poor for people with Schizophrenia in sustained attention tasks like Continuous Performance Task, where participants are required to attend to a series of letters or numbers and then to detect an intermittently presented target stimulus that appears on the screen along with the letters or numbers.
A large proportion of people with Schizophrenia also show eye-tracking dysfunction. In smooth pursuit of eye movement tasks involve tracking of a moving target like a pendulum, not only do people with schizophrenia show difficulties but at least 50% of the first-degree relatives of people with Schizophrenia also exhibit issues in eye-tracking. This suggests that disturbances in eye-tracking have a genetic basis.
However, the strongest finding in the area of neurocognition and Schizophrenia has been reported through the use of a psychophysiological measure called P50. In this measure when two clicks are heard in close succession (50 milliseconds), the brain produces a positive electrical response to each click. In typical participants, the response to the second click is less marked than the first click that is equal in Schizophrenia. The implication of this finding is that whereas a typical brain reduces responses to repeated sensory events, the brain of a person with Schizophrenia is unable to. As is the case in eye-tracking tasks, first-degree family members of patients with Schizophrenia are also more possibly than controls to have issues with P50 suppression.
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