Schizophrenia

• Schizophrenia is a serious mental disorder experienced by about 1% of the world population. It is more commonly diagnosed in men, city-dwellers, and lower socio-economic groups.
• Diagnosis and classification of schizophrenia go hand in hand, as to diagnose we need to distinguish between disorders (by identifying clusters of symptoms that occur together and classifying this as one disorder). Diagnosis is possible by identifying symptoms and deciding what disorder a person has.
• Two major systems for mental disorder classification:

  1. WHO International Classification of Disease (ICD-10) diagnoses schizophrenia if one positive symptom is present.
  2. Psychological Association Diagnosis + Statistical Manual (DSM-5) diagnoses schizophrenia if two negative symptoms are present.
• Positive symptoms can be described as additional experiences beyond those of ordinary existence. These are hallucinations and delusions.
• Hallucinations are unusual sensory experiences. Some may be related to events in the environment, while others may bear no resemblance to real-world events. These can be voices heard, often criticising the sufferer, or can be related to any sense e.g. seeing distorted faces.
• Delusions, also known as paranoia (irrational beliefs). Common delusions involve being an important historical, political, or religious figure. Delusions can also be being persecuted, by government/aliens/having superpowers. Another belief may be do with the body: believing they are under external control, which will seem very bizarre to onlookers.
• Negative symptoms of schizophrenia can be defined as the loss of usual abilities and experiences. This includes speech apathy and avolition.
• Speech poverty is changes in speech patterns, a reduction in amount and quality of speech, accompanied by a delay in verbal responses during conversation. More emphasis is now placed on speech disorganisation: speech becoming incoherent/a sufferer changing topic mid-sentence.
• Avolition, sometimes called apathy, is finding it difficult to keep up with a goal-directed activity, i.e. a loss of motivation. People with schizophrenia have sharply reduced motivation to carry out a range of activities. Andreasen (1982) identified three signs of avolition: poor hygiene and grooming, lack of persistence in work/education, lack of energy.
• A limitation of diagnosis and classification of schizophrenia is that Cheniaux found low inter-rather reliability in a study where he got 2 psychiatrists to independently diagnose 100 patients using both DSM and ICD criteria. The inter-rater reliability was poor, with one psychiatrist diagnosing 26 with Sz according to the DSM and 44 according to ICD, and the other diagnosing 12 according to the DSM and 24 according to the ICD. This means that diagnosis may not be a very reliable of straightforward process, too subjective in it’s nature.
• Counterpoint for inter-rather reliability: Osório et al took 180 pps and pairs of interviewers, finding inter-rater reliability to be at the 0.97 level, and the test retest at an 0.92 level. This supports the reliability of Sz diagnosis. Although, looking at the Cheniaux study, we can see that schizophrenia is much more likely to be diagnosed using the ICD than the DSM. This means that Sz is either over or under diagnosed according to the diagnostic systems, meaning the criterion validity is low.
• Co-morbidity (two conditions occurring together) is a problem for the diagnosis of schizophrenia as if two conditions occur together this calls into question the validity of their diagnosis and classification because they might just be a single condition. Buckley (2009) concluded that around half the patients with a Sz diagnosis also have depression or substance abuse issues. PTSD occurred in 29% of cases and OCD in 23%. This is a problem as it may mean that Schizophrenia may not exist as a distinct disorder and some people who have Sz may be misdiagnosed with a different disorder.
• Schizophrenia shares symptoms with other conditions, such as bipolar disorder (both have avolition and delusion symptoms), making diagnosis and classification unreliable. Under the ICD, a patient may be diagnosed with schizophrenia, while the DSM might classify them with bipolar disorder. This symptom overlap challenges the validity of schizophrenia as a distinct condition and highlights flaws in its diagnosis and classification.
• Longenecker (2010) found that since the 1980s, men have been diagnosed with schizophrenia more often than women, possibly due to genetic vulnerability. However, gender bias may also play a role. It appears that female patients typically function better than men, being more likely to work and have good family relationships (Cotton, 2009). This high functioning may explain why some women haven't been diagnosed while experiencing the same symptoms as men. This means women aren't receiving treatment and services that might benefit them.
• Black British and Americans are several times more likely to be diagnosed with Sz than white people. Given that the rates in Africa and the West Indies are not particularly high, this is almost certainly not due to genetic vulnerability. Cultural differences in interpreting symptoms, such as hearing voices, may contribute to this disparity. Escobar (2012) found that white psychiatrists often over-interpret symptoms and distrust black patients, suggesting that schizophrenia diagnosis may be influenced by cultural bias and discrimination.
• Family studies have confirmed that the risk of schizophrenia increases in line with genetic similarity to a relative with the disorder. Gottesman found a strong relationship between genetic similarity and schizophrenia in his large-scale study. He demonstrated how someone with an aunt with Sz has a 2% chance of developing it, increasing to a 9% chance if the individual has a sibling with Sz and 48% if they are an identical twin. Family shares aspects of the environment as well as genes, so correlation represents both.
• Schizophrenia is polygenic (many genes are involved). The most likely genes are those coding for neurotransmitters including dopamine.
• Ripke (2014) combined all previous data from genome-wide studies of schizophrenia. The genetic makeup of 37,000 people with a diagnosis of Sz was compared to that of 113,000 controls, 108 separate genetic variations were associated with slightly increased risk of schizophrenia.
• Different studies have identified different candidate genes, meaning that schizophrenia is aetiologically heterogenous (different combinations of factors, including genetic variation, can lead to the condition)
• Schizophrenia can also have a genetic origin in the absence of a Sz family history. Mutation in parental DNA can be caused by radiation, poison, or viral infection. Evidence for mutation comes from positive correlations between paternal age and Sz risk, increasing from 0.7% with fathers under 25 and 2% in fathers over 50 (Brown, 2002)
• The original dopamine hypothesis:

  Schizophrenia was thought to be the result of high levels of dopamine (hyperdominergia) in subcortical areas of the brain. For example, excess dopamine receptors in pathways from the subcortex to Broca's area may explain symptoms like speech poverty. Goldman-Rakic linked low levels of dopamine to negative symptoms.
• Davis (1991) proposed the addition of cortical hypodominergia i.e. abnormally low dopamine in the brain's prefrontal cortex could explain cognitive problems i.e. negative symptoms. It has also been suggested that cortical hypodominergia leads to subcortical hyperdominegria - so both high and low levels of dopamine in different brain regions are part of the updated dopamine hypothesis. As well as explaining links between abnormal dopamine levels and symptoms, current versions of the dopamine hypothesis try to explain the origins of abnormal dopamine function.
• Gottesman (1991) showed a strong link between genetic similarity and schizophrenia risk. Adoption studies (Tienari et al., 2004) confirm that children of sufferers remain at higher risk even in non-schizophrenic families. Molecular studies (Ripke et al., 1994) further identified genetic variations that increase susceptibility. While this supports a genetic basis for schizophrenia, the biological approach is deterministic, implying that biology alone dictates the likelihood of developing the disorder.
• There is strong evidence linking dopamine dysfunction to schizophrenia. Dopamine agonists like amphetamines worsen symptoms and can induce schizophrenia-like effects in non-sufferers (Curran et al., 2004), while antipsychotics reduce symptoms by lowering dopamine activity. Radioactive labeling studies (Lindstroem et al., 1999) show that schizophrenia sufferers produce dopamine more rapidly than controls, reinforcing dopamine's role in the disorder.
• There is also evidence to suggest that dopamine does not provide a complete explanation for Sz. Some of the genes identified in the Ripke et al. (2014) study code for the production of other neurotransmitters, so it appears that although dopamine is likely to be one important for Sz, so are other neurotransmitters. More recent research has shifted to investigate the role of a neurotransmitter called glutamate (Moghaddam & Javitt, 2012). The dopamine hypothesis acts as evidence for a central role of glutamate, meaning an equally strong case can be made for other neurotransmitters.
• Neural correlates are linked to both positive and negative schizophrenia symptoms, but causation is unclear. For example, reduced ventral striatum activity correlates with negative symptoms, but it's uncertain whether this causes the symptoms or results from them. A third possibility is that another factor influences both the negative symptoms and the ventral striatum activity. This uncertainty limits our understanding of schizophrenia’s origins, making effective treatment more challenging.
• Sz can take place in the absence of a family history of the disorder. One explanation for this is a mutation in parental DNA, for example, in paternal sperm cells. This can be caused by radiation, poison or viral infection. Evidence for the role of mutation comes from a study

  showing a positive correlation between paternal age (associated with increased risk of sperm mutation) and risk of Sz, increasing from around 0.7% in fathers under 25 to over 2% in fathers over 50 (Brown, 2002). This is support for the biological explanation as this would still impact the offspring genetically.
• The evidence supporting the role of biological factors in Sz is overwhelming. However, there is also evidence to suggest an important role for environmental factors, including psychological ones such as

  family functioning during childhood. After all, the probability of developing Sz even if your identical twin has it is less than 50% suggesting that other factors play a part. The clear evidence for environmental factors means biological factors alone cannot provide a complete explanation for Sz.
• The most common treatment for schizophrenia involves the use of antipsychotic drugs. Antipsychotics may be required in the short term or long term. These drugs can be divided into typical (traditional) and atypical (newer) or second-generation drugs.
• Typical antipsychotics have been around since the 1950s and include chlorpromazine, which can be taken as tablets, syrup, or by injection. Typical prescribed doses have declined over the last 50 years (Liv and de Haan 2009)
• Dopamine antagonists- there is a strong association between the use of typical antipsychotics and the dopamine hypothesis. Typical antipsychotics like chlorpromazine work by acting as an antagonist to the dopamine system. Antagonists are chemicals which reduce the action of a neurotransmitter, in this case, dopamine.
• Dopamine antagonists work by blocking dopamine receptors in the synapses of the brain, reducing the action of dopamine. When an individual starts taking chlorpromazine, dopamine levels build up, but then production is halted. According to the dopamine hypothesis, the dopamine-antagonist effect normalises neurotransmission in key areas of the brain, reducing symptoms like hallucinations.
• Sedation effect- chlorpromazine is also an effective sedative, which is believed to be related to it's effect on histamine receptors but it is not fully understood how this leads to sedation. Chlorpromazine is often used to calm individuals with many conditions. This has often been done when patients are first admitted to hospitals and are nervous.
• The aim of developing newer antipsychotics was to maintain or improve upon the effectiveness of drugs in suppressing the symptoms of psychosis and also minimise side effects.
• Clozapine was developed in the 1960s and trialled in the 1970s. It was withdrawn momentarily after the deaths of some patients from blood conditions. In the 1980s it was discovered to be more effective than typical antipsychotics. Due to its potentially fatal side effects, clozapine is not available as an injection. Clozapine binds to dopamine receptors just like chlorpromazine does, but it also acts on serotonin and glutamate receptors.
• Clozapine is believed to help improve mood and reduce depression and anxiety in patients, and that it may improve cognitive functioning. The mood-enhancing effects of this drug mean that its sometimes prescribed when an individual is on suicide watch. This is important as 30 to 50% of Schizophrenic patients attempt suicide at some point
• Risperidone was developed in the 1990s and aimed to reduce the harmful side effects of clozapine. Risperidone is believed to bind to dopamine and serotonin receptors, more strongly than clozapine. It is much more effective in smaller doses than most antipsychotics. There is some evidence to suggest that this leads to fewer side effects.
• Thornley et al. (2003) reviewed 13 trials with 1121 participants, showing that Chlorpromazine improved overall functioning and reduced symptom severity compared to a placebo, as well as a lower relapse rate in three trials. Meltzer found that Clozapine is more effective than both typical and other atypical antipsychotics, with effectiveness in 30-50% of treatment-resistant cases. Comparisons between Clozapine and other atypical antipsychotics, like Risperidone, were inconclusive.. This evidence supports the effectiveness of antipsychotics and means that, as far as we can tell, they work.
• Typical antipsychotics cause side effects like dizziness, agitation, sleepiness, weight gain, and itchy skin. Long-term use can lead to tardive dyskinesia (involuntary facial movements). The most serious side effect is neuroleptic malignant syndrome (NMS), which can cause high fever, delirium, coma, and be fatal, though it's now rarer due to lower doses. The serious side effects associated with antipsychotics means that they can do harm as well as good, and individuals may avoid this type of treatment as a result.
• The dopamine hypothesis suggests that high dopamine activity in the brain's subcortex contributes to schizophrenia (Sz). However, evidence shows that this theory doesn't fully explain the condition, as dopamine levels in other brain areas may be too low. This challenges how antipsychotics, which reduce dopamine, effectively treat schizophrenia, maybe they don't work in the way we initially thought. The unclear mechanism behind antipsychotics raises concerns about their effectiveness, suggesting other factors may contribute to their success.