Schizophrenia Schizophrenia is a serious mental disorder affecting approximately 1% of the worlds population. It is characterised by three types of symptoms, positive symptoms, negative symptoms and cognitive symptoms. Contrary to the popular usage of the word, schizophrenia does not present with a split personality.
Introduction to SchizophreniaThe neurobiological basis of schizophrenia is still not fully understood, however there are theories supported by evidence from certain pharmacological responses and brain imaging technologies that provide some insights into this area. While the positive symptoms experienced by schizophrenics are the most distinctive and is the common perception of the disorder, positive symptoms tend to be episodic and present later in the development of the disorder than the more chronic negative and cognitive symptoms.
Causes of SchizophreniaThe exact causes of schizophrenia remain unknown, but a number of risk factors for the development of the disorder have been identified. Schizophrenia appears to follow the diathesis-stress model in which an underlying tendency toward the disorder and psychosocial environmental factors together contribute to the development of the disorder.
HeretabilitySchizophrenia is known to be highly heritable, with separate twin studies conducted in England and Finland estimating a heritability of around 83%. No single gene has been identified as a "schizophrenia gene" but many genes have been identified as increasing the likelihood of the development of schizophrenia. The DISC1 gene is one such gene mutation found often in families with high incidence of schizophrenia. The DISC1 gene is involved in developmental and adult neurogenesis. The presence of this mutation increases the liklihood of the development of schizophrenia by a factor of 50. It is also linked to the development of several other mental disorders including bipolar, depression and autism.
Paternal age is another known heritability factor. Children of an older father are more likely to develop the disorder. This is believed to be related to mutations of the spermatocytes, which divide every 16 days after puberty. The rapid division of cells increases the likelihood of mutation in the cells.
Some researchers believe epigenetic factors may contribute to the development of the disorder. Epigenetics controls the expression of genes. Groups of atoms may attach themselves to the histone proteins around which DNA strands are wound, causing the promotion or inhibition of the gene expression. Epigenetic changes may be triggered by environmental factors such as toxins.
Environmental factorsA number of environmental factors have been correlated with the development of schizophrenia. It is not clear how some of these factors contribute to the disorder. The known environmental factors are:
- Season of birth. Children born in late winter or early spring are more likely to develop the disorder. Studies of this seasonal effect have been replicated in both the northern and southern hemispheres, with the late winter/early spring birth being correlated.
- Viral infection during pregnancy. Children of mothers who are infected with viruses during pregnancy are more likely to develop the disorder.
- Vitamin D deficiency. 
- Population density. 
- Prenatal malnutrition. 
- Tobacco smoking. Studies found that second hand smoke alone was sufficient to increase the likelihood of the development of the disorder. 
- Homes high in expressed emotion. This is the tendency of families to criticise and express hostile emotion towards one another. Family dynamics such as this have been linked to the development of the disorder.
- Cannabis use. "During adolescence, cannabis consumption is correlated with a significantly increased likelihood and severity of emergence of schizophrenia  and cannabis use is a significant prediction factor for the development of schizophrenia . Cannabis consumption prior to the age of 18 more than doubles the risk of schizophrenia in a large-cohort of non-predisposed persons ; the rate of development is nearly six-fold with heavy use which is a similar rate seen in so-called predisposed individuals."
Symptoms & Types/Variations of SchizophreniaSchizophrenia is characterised by a triad of symptom types, positive, negative and cognitive. Typically the symptoms develop over a period of several years with negative symptoms appearing first, followed by cognitive symptoms and eventually positive symptoms.
Positive symptomsPositive symptoms are so named because they involve the addition of something not usually present.. Positive symptoms include hallucinations, delusions and disorganised thinking with a loosening of lines of association.
Hallucination - Hallucinations are perceptual disturbances that distort or have no basis in reality. While they are commonly portrayed as visual disturbances they can be of any sense and auditory hallucinations are much more common than visual hallucinations.
Delusion - Delusions are false beliefs that remain firmly held to despite contradictory evidence.
Loosened lines of associations - An individual experiencing psychosis may express themselves more metaphorically without the intention to do so. For example, a rational person might describe a friend by saying "Joe was irritable". With a loosening of lines of association a psychotic person might associate irritable with an animal notorious for irritability and say "Joe was a rhinoceros".
Negative symptomsNegative symptoms are so named because they involve the absence of behaviours that are normally present. Negative symptoms include flattened emotional responses, anhedonia, lack of motivation, poverty of speech and social withdrawal.
Cognitive symptomsCognitive symptoms include lack of psychomotor speed, difficulty sustaining attention, learning deficits, trouble with problem solving and difficulty with abstract thought. These symptoms may be produced by the same brain regions as negative symptoms.
Treatments of Schizophrenia
CannabidiolThere is emerging evidence that CBD may have some application as a natural antipsychotic. Please note, this research applies to CBD, not to the entire cannabis plant. Cannabis use in the developing brain has been correlated with increased instances of schizophrenia, in a dose dependent correlation 
PsychotherapyThere is some evidence of efficacy using various forms of psychotherapy to manage symptoms of psychoses and prevent relapse.
AntipsychoticsSince the discovery of chlorpromazine and the subsequent development of other antipsychotic medications these drugs have been the treatment of choice for schizophrenia. Antipsychotic medications are very effective for reducing or eliminating episodes of positive symptoms. The use of antipsychotic medications to treat schizophrenia however tends to cause a worsening of negative and cognitive symptoms. Some of the newer second generation (atypical) antipsychotic medications such as aripiprazole exert a partial agonist rather than the antagonist effect exerted by other antipsychotics on the dopamine receptors involved in schizophrenia and may be less detrimental to the negative and cognitive symptoms.
The use of antipsychotics as a default option to treat schizophrenia has been criticised in recent years with some studies finding that schizophrenics may have better outcomes without the medications.. Studies have also identified high levels of non-compliance with medication attributed to inefficacy or intolerable side effects and a need for more research into effective treatments for negative symtoms of the disorder.
Neurobiological basis of Schizophrenia
The dopamine hypothesisWhile the exact mechanisms of schizophrenia are not fully understood, there is substantial evidence for the role of over-activity of dopamine synapses in the mesolimbic pathway in the development of positive symptoms.
In the middle of the twentieth century the first antipsychotic medication, chlorpromazine was discovered which was found to have a dramatic effect on eliminating or diminishing the positive symptoms (those associated with psychosis) of schizophrenia. Other antipsychotics have since been developed with similar effects. The commonality between the drugs is that they all block the activity of dopamine D2 and D3 dopamine receptors.
It has similarly been identified that another category of drugs exacerbates and triggers the positive symptoms of schizophrenia. That category of drugs is stimulants, which includes cocaine and amphetamines. Stimulants increase activation of dopamine synapses by causing increased levels of dopamine release.
Dopamine is a neurotransmitter that has a vital role in the reinforcement of behaviour in learning. It has been suggested that positive symptoms may be a consequence of the unintended reinforcement of the kind of irrational thoughts we all have from time to time, but usually dismiss. Paranoid delusions may be the result of increased dopaminergic transmission to the amygdala. The amygdala is a limbic system structure that receives strong dopaminergic projections from the mesolimbic pathway, and is involved in conditioned responses to aversive stimulus (fear etc).
While the dopamine hypothesis presents a plausible model of how positive symptoms of schizophrenia are caused, and is supported in those assertions with evidence, it is unable to adequately explain negative and cognitive symptoms. Studies have indicated that the cause of these symptoms originates in a different brain region - the prefrontal cortex. It has been found that dopamine activity in this area of the brain is reduced in schizophrenics, which is the reason antipsychotics may worsen those symptoms. This has led researchers to look for more complete explanations of the disorder and the development of the glutamate hypothesis.
The glutamate hypothesisIt was suggested in 1998 that hypofrontality (a decrease in activity in the prefrontal cortex) may be responsible for the negative and cognitive symptoms of schizophrenia.. As with the case of the dopamine hypothesis, researchers were led to examine substances that caused similar symptoms as a method of understanding how the disorder works. Both PCP and ketamine are indirect NMDA glutamate antagonists, and both drugs can temporarily cause the same positive, negative and cognitive symptoms of schizophrenia in healthy individuals.
PCP and ketamine cause a suppression of activity in the dorsolateral prefrontal cortex and also decrease dopamine utilisation in this area of the brain. Suppression of these neurotransmitter systems causes hypofrontality. The dorsolateral prefrontal cortex is an area of the brain involved in the regulation of the mesolimbic pathway, and so a deficit in activity in this region may cause a surplus of activity in the mesolimbic pathway, accounting for the positive symptoms of schizophrenia consistently with the dopamine hypothesis.
One theory tested in an animal study is that DISC1 gene mutations suppress the expression of the gene, which causes abnormalities to appear in pyramidal neurons of the prefrontal cortex and the mesocortical dopaminergic system, resulting in reduced dopaminergic transmission to the prefrontal cortex and behaviour consistent with that schizophrenia. Thus abnormalities in the pyramidal neurons of the prefrontal cortex are the primary cause of schizophrenic symptoms if this theory is correct.
A second theory also tested in an animal study is that hypofrontality is caused by decreased GAGAergic inhibition in the dorsolateral prefrontal cortex, resulting in electrical rhythm disruption of the region and consequent neural abnormalities. The theory was tested by introducing a targeted virus to test mice that caused increased expression of dopamine D2 receptors in the striatum. This increased receptor expression caused deficits in GABAergic transmission in the prefrontal cortex.
The Dangers & Health Risks of SchizophreniaOnly 10-20% of schizophrenics ever fully recover. More than half fail to achieve even moderate improvement, and of those that do most relapse within a year. Early identification of the disorder and treatment is predictive of improved outcomes.
Schizophrenics may experience confusion and paranoia due to the symptoms currently being experienced. In such states they may constitute a danger to themselves or others. A delusional schizophrenic may be adjudged as not having the capacity to refuse treatment, and consequently treated without their consent.
More Schizophrenia Sections
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- ^Niwa, M., Kamiya, A., Murai, R., Kubo, K., Gruber, A. J., Tomita, K., … Nabeshima, T. (2010). Knockdown of DISC1 by In Utero Gene Transfer Disturbs Postnatal Dopaminergic Maturation in the Frontal Cortex and Leads to Adult Behavioral Deficits. Neuron, 65(4), 480-489. doi:10.1016/j.neuron.2010.01.019
- ^Li, Y., Kellendonk, C., Simpson, E. H., Kandel, E. R., & Gao, W. (2011). D2 receptor overexpression in the striatum leads to a deficit in inhibitory transmission and dopamine sensitivity in mouse prefrontal cortex. Proceedings of the National Academy of Sciences, 108(29), 12107-12112. doi:10.1073/pnas.1109718108 Categories: Category Mental Disorders
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