What We Know So Far About Schizophrenia
Schizophrenia is one of the most severe mental disorders. Not everyone with the disorder does poorly though. However, 50% of suffers have on-and-off problems with it in the long term. About 20% have chronic symptoms and disability.
Unemployment is really high at 80 to 90%. A shorter life span, about 10 to 20 years shorter, is also common. It is estimated that the total cost of caring for patients is more than $60 billion a year (US). This number includes "both direct health care costs and also indirect economic losses from unemployment and early death."
There are three main categories of symptoms: positive, negative and cognitive.
Positive symptoms are when reality is distorted in patients. They experience hallucinations, and delusions. Thought disorganization is another positive symptom.
Negative symptoms affect normal emotions and behaviour, and may be confused for depression. These include reduced expression of emotion ("speaking without moving or with monotonous voice"), loss of motivation, and social withdrawal.
Cognitive symptoms include poor executive function, that is, "understanding information and using it to make decisions." Reduced attention span and impaired memory are also additional cognitive symptoms.
There are currently no diagnostic tests or biomarkers available. Diagnosis is made clinically by examining patient history and mental state. Criteria for the disorder is defined in the Statistical Manual of Mental Disorders (DSM-5). To be diagnosed with schizophrenia, a patient must present with specific characteristic symptoms of schizophrenia for at least 6 months, combined with a disruption in social or occupational function, and must not have another diagnosis that could explain the symptoms.
Schizophrenia has a high heritability. This means that genes play a large role in the disorder. Heritability estimate for schizophrenia is roughly 80%. Interestingly, in identical twin studies, if one twin develop schizophrenia, the other twin has a 50% chance of also developing the disorder.
Schizophrenia likely involves many genes. Looking for the "schizophrenia genes" has been difficult to achieve. Initial linkage studies that looked for gene associated with schizophrenia identified candidate genes including the dopamine receptor and glutamate receptor to name a few.
Microdeletion and microduplication have been observed to be three times more common in schizophrenia patients compared to control. These were found in genes that are unregulated in pathways related to brain development. Micro deletions and duplications in chromosomes 1, 2, 3, 7, 15, and 16 have also been linked to schizophrenia.
In 2014, a genome-wide association study identified 108 single-nucleotide polymorphisms (SNPs) that were associated with schizophrenia. The SNPs were found in genes encoding for neurotransmitter signalling pathways, including dopamine (D2 receptor) and also glutamate (NMDA receptors). However, these SNPs confer only a tiny risk for the disorder.
More recently, in 2016, a study looked at the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus - an area on chromosome 6 that is involved in immune function. The researchers focused on complement component 4, or C4, an MHC gene. They found that alleles which promoted greater expression of a C4 gene in the brain were associated with a greater risk of the disorder. When researchers probed further, C4 was found to be involved in the elimination of synapses during brain maturation (in mice). "Synaptic pruning" is most active during late adolescence in humans, when the onset of symptoms of schizophrenia typically occur. Hence, the inheritance of this C4 gene could lead to increased synaptic pruning, which may increase the risk of schizophrenia.
For the last three decades, the neurodevelopment hypothesis was what was used to explain the contribution from the environment. This hypothesis says that factors that affect early brain development during pregnancy can result in higher risk of schizophrenia. These include maternal stress, infections, nutritional deficiencies, intrauterine growth retardation, and pregnancy and birth complications.
Other risk factors, like socioeconomic factors, childhood adversity, and immigration are also associated with the disorder. Childhood adversity refers to sexual, physical, and emotional abuse, neglect, bullying and the losing one or both parents. Being born in late winter or early spring, or being born or raised in cities are also associated with high rates of schizophrenia. Cannabis use in adolescence is also thought to be a risk factor. Additionally, head injury, epilepsy, autoimmune diseases and severe infections have also been associated with increased risk of the disorder.
The cause of schizophrenia is currently unknown. Here are just some of the possible underlying causes.
Schizophrenia may arise from altered structure and function of particular brain regions. There is evidence that the prefrontal cortex may be involved in specific cognitive deficits such as memory and executive function.
Many studies have implicated the abnormal function of the dopamine pathway in generating psychotic symptoms including delusions and hallucinations. However, the dopamine abnormality can't explain the full range of clinical features of schizophrenia.
Studies have also suggested that disturbed glutamate function might contribute to negative and cognitive symptoms.
Antipsychotics are the go-to treatment for schizophrenia. Almost all antipsychotic drugs work by blocking dopamine receptors. Antipsychotics are good at reducing the positive symptoms like auditory hallucinations and delusions. But they are not effective at treating the negative or cognitive symptoms. These two symptoms matter more as they affect a person's ability to function on a daily basis.
Adverse side effects are common with antipsychotics, and they include weight gain, movement disorders, and sedation. These lead to poor compliance with the drugs. Newer, "second generation" antipsychotics are effective for psychotic symptoms with fewer movement disorder, but are associated with metabolic side effects like increased cholesterol.
In addition to drugs, treatment may also include counselling and other types of psychosocial therapy. A multidisciplinary team may be involved in helping patients integrate back into the community, finding work or get back into school. Cognitive behavioural therapy can also lessen both symptoms and suffering, but at the moment it is quite controversial.
Most scientists believe that schizophrenia is caused by an interplay of genes and the environment. Fittingly, new research must incorporate both these aspects. Such studies are harder but should be undertaken.
Although we may not understand what causes this complex disorder, we at least have relatively effective treatments for it. Treatment isn't perfect though as it comes with troublesome side effects. Let's hope that the next generation of drugs not only be effective but also come with fewer side effects.
Balter M. Schizophernia's Unyielding Mysteries. Scientific American. May 2017: 55-61. Print.
Dean L. Schizophrenia. 2017. In: Pratt V, McLeod H, Dean L, Malheiro A, Rubinstein W, editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-
Owen MJ, Sawa A, Mortensen PB. Schizophrenia. 2016. Lancet. 388:86-97
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