What is the schizophrenia cause? This is the answer which every patient and family member asks. The answer to this has however not been unequivically resolved. Researchers have identified a number of factors to be implicacted in the development of schizophrenia.
Most evidence points to there being a biological schizophrenia cause. The final common pathway appears to involve altered dopamine neurotransmission in certain areas of the brain. This reductionist theory developed after it was observed that there was an improvement in patients with schizophrenia after they were administered chlorpromazine to treat anxiety. The main action of chlorpromazine is at the dopamine 2 (D2) receptor, and this is the one common mechanism of action which has been shared by all subsequent antipsychotics with various actions at the D2 receptor. It was observed that the more potent the interaction (blockage) was at the D2 receptor, the more effective it was at reducing symptoms. On the other hand, it was also observed that drugs which stimulate the D2 receptor can cause psychotic symptoms. This has been supported by a large body of studies which has studied receptor profiles, dopamine and dopamine metabolite concentrations, and dopamine transporter proteins.
But what is causing this altered dopamine neurotransmission? The main theory is that this comes about as result of a complex interaction between the patient's genetic make-up, the environment and social influences.
There is strong evidence for genetic vulnerability as a schizophrenia cause. This is deduced from various findings. It has been observed that there is a strong familial component to schizophrenia, ie it runs in families and rates of schizoophrenia are higher in relatives of patients than in the general population. The prevalence of schizophrenia in the general population is 1% and increased as one gets closer genetically to the schizophrenia patient. In a sibling this prevalence is 8%. In children with one parent with schizophrenia it is 12%. In a non-identical twin of a schizophrenia patient it is 12%. If there are two parents with schizophrenia, the incidence increases to 40%. The prevalence in the identical twin of a schizophrenia patient is close to 50%. The transmission does not however follow simple Mendelian inheritance, and there is probably multiple susceptability genes, each with a small effect and acting with environmental factors.
This was further supported by twin studies in which identical twins were separated at birth through adoption and reared apart, where the rates of schizophrenia were the same for both groups. This suggests that the genetic influence is stronger than the environmental influence.
Studies in early-onset schizophrenia (before age 17yr) also show a familial clustering of deficits and psychotic disorders in families of schizophrenia patients, further suggesting a genetic influence. There are higher rates of certain chromosomal abnormalities. Neurocognitive deficits and eye movement dysfunction are found in some relatives. Certain genes have been found with increased incidence in families with schizophrenia.
There are findings from studies which strongly suggest that schizophrenia is a neurodevelopmental problem. Patients with schizophirenia often have language development abnormalities growing up, do poorly at school, have decreased IQ scores, have motor co-ordination problems and are clumsy. They may also have been socially maladjusted, odd or socially withdrawn, and globally poorer functioning than their peers. Schizophrenia forms part of a group of disorders charcterised as neurodevelopmental disorders by virtue that it shares what is known as copy number variants (CNVs). These disorders include epilepsy, attention deficit disorder (ADD or ADHD), autism and learning disability which has been recognised as occurring frequently in children. CNVs are micro-abnormalities of the DNA, which can result in alterations of the genes.
Studies comparing first-episode psychosis, with high at-risk groups and normal controls show that both first-episode cases and high at-risk cases have deficits in higher executive functioning, but less severe in the high at-risk group. The conclusion from this is that these deficits are present before the diagnosis of schizopohrenia.
Neuro-imaging and functional studies also support a biological basis as a schizophrenia cause. Studies in medication-free first-episode cases show brain changes. Increased ventricles and reduced grey matter volume in certain regions concerned with emotional and higher cognitive processing are the most confirmed findings. This seems to be maintained later in life as it is seen in chronic schizophrenia patients as well. The se changes have also been noted in unaffected family members. Studies looking at duration of untreated psychosis have shown that there are greater reductions in grey matter volume, the longer patients remain untreated. This suggests that psychosis is toxic to the brain.
Functional studies looking at dopamine activity in individuals at high risk for schizophrenia, have found similar changes to that of indiviuals with established schizophrenia. Studies continue to find evidence of altered dopamine functioning in untreated first episode individuals compared to controls. PET and SPECT studies have shown altered D2 receptor functioning during relapses of pscyhosis. It is thought that dopamine is critical in at least the positive symptoms of schizophrenia.
Cannabis is strongly associated with schizophrenia. It results in a 2 to 3% increase in the prevalence of schizophrenia but only with heavy cannabis use which starts in early teenagehood. Cannabis is also known to cause psychotic symptoms in some individuals without a psychotic disorder, and can result in relapse in established cases of schizophrenia. Again there is a tendency for cannabis to cause psychosis in genetically vulnerable individuals.
There is less evidence that other drugs such as heroin, amphetamines, cocaine and alcohol are causal in the development of schizophrenia but use of these drugs can cause psychosis.
There are other factors as to the schizophrenia causeSeason of birth
Higher population density such as in poorer, inner city populations are more at risk. Rates are higher in cities compared to rural areas.
Social deprivation and poverty are also associated as being as a schizophrenia cause. There are 2 theories for this.
The Social Drift theory postulates that the occupational and social impairment caused by the illness causes the affected person to fall to a lower socioeconomic group.
The Social Causation theory states that it is the stress experienced by mebers of the lower socioeconomic groups that contributes to the development of schizophrenia.
Finally, there is no one theory as to the schizophrenia cause. There is good evidence that it is due to genetic vulnerability, but that the expression of schizophrenia results from a complex interaction between genetic factors, epigenetic and psychosocial factors.
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Synopsis of Psychiatry. Kaplan & Sadock