Biological Explanations and Treatments for Schizophrenia Flashcards
Gottesman 1991
Family study
• identical twins are much more likely to have schizophrenia if their twin has it- 48% of identical twins with schizophrenia have a twin who is also diagnosed
• fraternal twins were less than half as likely (17%)
• although, not 100% of identical twins share schizophrenia, suggesting that the environment plays a factor
• the greater the risk of genetic relatedness, the greater the risk of developing schizophrenia
Heston 1996
compared 47 adopted children whose biological mother had schizophrenia with a control group of adopted children with no history of schizophrenia in their biological family
• none of the control group was diagnosed with schizophrenia; 16% of the offspring of mothers with schizophrenia were diagnosed
Tienari et al. (2000)
Adoption study
11% of 164 adoptees whose mothers have schizophrenia
Candidate gene for schizophrenia
• schizophrenia is thought to be polygenic- Aetiologically heterogeneous
• Ripke et al. (2014) completed a study combining all data from a genome wide study of schizophrenia
-37,000 patients were compared to 113,000 controls; 108 separate genetic variations were associated with an increased risk of schizophrenia
The Dopamine hypothesis general
• an excess of the neurotransmitter dopamine has been implicated in the symptoms of schizophrenia
• hyperdopaminergia in the subcortex
• hypodopaminergia in the cortex
Hyperdopaminergia in the subcortex
(old hypothesis)
• higher levels of dopamine in the subcortex
• excess levels of dopamine receptors in Broca’s area
• causes poverty of speech and experience of auditory hallucinations
• the dopamine hypothesis states that messages from neurons that transmit dopamine fire too easily or too often, leading to the characteristic symptoms of schizophrenia (older hypothesis)
• people with schizophrenia are thought to have abnormally high numbers of D2 receptors on receiving neurons, resulting in more dopamine binding and therefore more neurons firing
Hypopdopaminergia in the cortext
• abnormal dopamine systems in the brain’s cortex (new hypothesis)
• Goldman-Rakic et al. (2004) identified a role for low levels of dopamine in the prefrontal cortex
• can cause negative symptoms of schizophrenia as it effects thinking and decision making
Evidence for the dopamine hypothesis
• Amphetamines; this is a dopamine agonist, stimulating nerve cells containing dopamine causing the synapse to be ‘flooded’- large doses of the drug can cause hallucinations and delusions
• Cocaine; also increases the levels of dopamine in the brain and can cause the positive symptoms of schizophrenia and exaggerate them in people who already have schizophrenia
• an agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell
• an antagonist blocks or reduces the effect of a neurotransmitter
Neural Correlates of Schizophrenia
• neural correlates are measurements of the structure or function of the brain that occur in conjunction with an experience, in this case schizophrenia
• there is growing evidence that schizophrenia is down to structural abnormalities in the brain
• brain scanning techniques have made it possible to investigate living brain images
• both positive and negative symptoms have neural correlates
• people with schizophrenia have abnormally large ventricles in the brain. Ventricles are fluid filled cavities. This means that the brains of people with schizophrenia are lighter than normal.
Neural correlates of Schizophrenia’s negative symptoms
• activity in the ventral striatum has been linked to the development of avolition (loss of motivation)
• the ventral striatum are believed to be particularly involved in the anticipation of a reward for certain actions
• Juckel et al. (2006)- lower levels compared to controls
• negative correlation between activity levels in the ventral striatum and the severity of overall negative systems
Nerual correlates of schizophenia’s positive symptoms
• reduced activity in the superior temporal gyrus and anterior cingulate gyrus have been linked to the development of auditory hallucinations
• patients experiencing auditory hallucinations showed lower activation levels in these areas than controls
• therefore, reduced activity in these areas of the brain is a neural correlate of auditory hallucinations
• (Allen et al., 2007)
(Evaluations of Biological Explanations) Multiple sources of evidence for genetic susceptibility
• genetic links- Gottesman (1991)
• adoption studies- Tienari et al. (2004)
• genetic variation- Ripke et al. (2014)
(Evaluations of Biological Explanations) Mixed evidence for the dopamine hypothesis
• Curran et al. (2004) found that dopamine agonists increase the levels of dopamine and can make the symptoms of schizophrenia worse
• Tauscher et al. (2014) found that antipsychotic drugs reduce the levels of dopamine
• Lindstoroem et al. (1999) found that the chemicals needed to produce dopamine are taken up faster in the brains of people with schizophrenia, suggesting they produce more dopamine
• Moghaddam and Javitt (2012) have found evidence for the role of a neurotransmitter called glutamate
(Evaluation of Biological Explanations) The role of mutation
• there is evidence of mutations in parental DNA- paternal sperm
• caused by radiation, poison or viral infection
• Brown et al. (2002)- positive correlation between paternal age and risk of schizophrenia
• increasing from around 0.7% fathers under 25 and 2% in fathers over 50
Drug Therapy
• the majority of people with schizophrenia will follow drug therapy
• antipsychotic drugs (also called neuroleptics) were discovered in the 1950s
• they are a group of psychoactive drugs which alter brain function and result in changes to perception and behaviour
Antipsychotics
drugs used to reduce the intensity of symptoms, in particular, the positive symptoms of psychotic conditions like schizophrenia
• Typical antipsychotics: the first generation of antipsychotics (developed during the 1950s). They work as dopamine antagonists (e.g. Chlorpromazine)
• Atypical antipsychotics: second generation of antipsychotics (developed during the 1990s). They typically target a range of neurotransmitters such as dopamine and serotonin (e.g. Clozapine and Risperidone)
(typical antipsychotics) Chlorpromazine
• taken daily with a dose up to 1000mg. Typical doses are 400-800mg and this has decreased over the last 50 years (Liu and de Haan 2009)
• Strong association between chlorpromazine and the dopamine hypothesis- antagonists
• initially the dopamine builds up in the brain, then production is reduced
• according to the hypothesis, this dopamine-antagonist effect normalises neurotransmission- reducing symptoms such as hallucinations
• is a sedative- it effects the histamine receptors
• used to calm patients especially when admitted to hospital
(atypical antipsychotics) Clozapine
developed in the 1960s and trialled in the early 70s
• used when other treatments have failed
• daily dosage is between 300 and 450mg per day, lower than Chlorpromazine due to the fatal side effects
• binds to dopamine receptors, similarly to chlorpromazine, however, it also acts on serotonin and glutamate receptors, Helps mood and reduces depression and anxiety
• can only be taken by tablets to avoid higher risk of side effects on the blood (agranulocytosis)
(atypical antipsychotics) Risperidone
developed in the 1990s as an attempt to reduce side effects of clozapine
• smaller doses are given from 4-8mg up to 12mg per day
• binds to dopamine and serotonin receptors
• However, it has a stronger binding effect on dopamine than clozapine and is effective in lower doses
(Evaluations of Biological Treatments) Evidence for effectiveness
• Thornley et al. (2003) reviewed studies comparing the effects of chlorpromazine to control conditions- patients in this condition received a placebo
• Data from 13 trials with a total of 1121 participants showed that chlorpromazine was associated with better overall functioning and reduced symptom severity
• Data from three trials with 512 participants show that relapse rates were also lower when the drug was taken
(Evaluations of Biological Treatments) Atypical antipsychotics
• Meltzer (2012) concluded that clozapine is more effective than typical antipsychotics and other atypical antipsychotics
• effective in 30-50% of treatment-resistant cases
• Meltzer also stated that other atypical antipsychotics have been developed to reduced side effects and have succeeded (risperidone)
(Evaluations of Biological Treatments) Serious side effects
• some side effects are mild but they can be fatal: dizziness, agitation, sleepiness, stiff jaw, weight gain, and itchy skin
• neuroleptic malignant syndrome: where the drugs block the dopamine in the hypothalamus: hight temperature, delirium, coma and death
• Tardive Dyskinesia (uncontrollable movements of the face, lips, mouth, tongue as well as other body areas)
• Agranulocytosis: a deficiency of granulocytes in the blood, causing increased vulnerability to infection, due to a decrease of white blood cell production
(Evaluations for Biological treatments) Use of antipsychotics depends on the dopamine hypothesis
• much higher levels of dopamine activity in the subcortex
• however, not a complete explanation for schizophrenia
• levels were too low (in other parts of the brain) rather than too high
(Evaluations for Biological treatments) The Chemical Cosh Argument
• NICE recommend using antipsychotics to calm patients, but could this be a benefit to staff rather than to patients?
• could sedating patients be a human rights issue and is it unethical?
(Evaluations for Biological treatments) Problems with the evidence
• Healy (2012) has suggested that over publication has lead to misleading positive evidence
• due to the drugs calming effects, it can be concluded that they help patients with schizophrenia, but do they actually reduce the severity of psychosis?
• most publications discuss short term rather than long term benefits and compare those that have started taking them after withdrawal
