A biological explanation for schizophrenia L.O. To be able to describe and evaluate the dopamine hypothesis of schizophrenia

Schizophrenia: brain chemicals We know what the neurotransmitter acetylcholine does in the nervous system……. But how might neurotransmitters be implicated in mental illness?

Neurones Source: science photo library Neuronal cell bodies Synapses occur at the junctions Axons

Synapses Neurones transmit signals electrically along their axons The synapses (junctions between neurones) transmit signals chemically

Synapse Vesicles filled with neurotransmitter Location of receptors (post- synaptic density) Synaptic cleft Source: neuroscience.wustl.edu

Dopamine animation

Vesicles release neurotransmitter into synaptic cleft

Neurotransmitter binds to receptors & activates them

Enzymes are released to break down the neurotransmitter

Excess neurotransmitter is taken up by the pre-synaptic neurone

Vesicles are replenished with new & reused neurotransmitter

The dopamine hypothesis Schizophrenia is caused by excessive activity at synapses that use dopamine as their primary neurotransmitter This causes abnormal functioning of DA- dependent brain systems, resulting in schizophrenic symptoms

Schizophrenia & dopamine The dopamine hypothesis: Schizophrenia is caused by excessive DA activity. This causes abnormal functioning of DA- dependent brain systems, resulting in schizophrenic symptoms DA can increase or decrease brain activity depending on the system you’re looking at

Positive and negative INCREASE IN DOPAMINE IN THE MESOLIMBIC SYSTEM INCREASE IN DOPAMINE IN THE MESOCORTICAL SYSTEM POSITIVE SYMPTOMS OF SCHIZOPHRENIA NEGATIVE SYMPTOMS OF SCHIZOPHRENIA

Examination question – describe Describe one explanation for schizophrenia. (4 marks) Dopamine: Excess dopamine in the brain possibly causes schizophrenia/eq; There is an increase of activity at dopamine synapses/eq; This is associated with increased feelings of paranoia/eq; It also explains why hallucinations may occur as the brain is too active/eq; Over stimulation of the mesolimbic pathway is thought to be linked to positive symptoms of schizophrenia/eq; Problems with dopamine functioning in the pathway connecting the midbrain to the frontal lobes is associated with negative symptoms

Evaluation of the dopamine hypothesis

Who would you rather be for the day…….? OR …….why?

Interview _bNsajY _bNsajY

Lindstroem et al. (1999) Evidence for the dopamine hypothesis is mixed. There is certainly evidence to suggest that dopamine levels are higher in the brains of people with schizophrenia. In one study Lindstroem et al. (1999) radioactively labelled a chemical called L-DOPA, which is used by the brain to produce dopamine. They administered the L-DOPA to ten untreated patients with schizophrenia and a control group of ten people with no diagnosis. Using a brain scanning technique called PET scanning; they were able to trace what happened to the L- DOPA. The L-DOPA was taken up more quickly in the patients with schizophrenia, suggesting that they were producing more dopamine than the control group.

Lewine (1990) Folens p141 – classic research – use this to fill out p39 (MRI) of your workbooks.

The dopamine hypothesis Wise & Stein (1973) report abnormally low levels of DBH in post-mortem studies of S patients Would suggest abnormally high DA activity as DBH needed to break DA down Can’t rule out cause of death or post-mortem changes as a source or error

The dopamine hypothesis Overdose of amphetamine (DA agonist) can produce S-like symptoms. S patients have abnormally large responses to low amphetamine doses Suggests a role for DA in S symptoms Suggests that the issue is over-sensitivity to DA rather than excessive DA levels

Synoptic - Making Connections Make a connection between: Eye Witness Testimony Rosenhan

The dopamine hypothesis S symptoms can be treated with DA antagonists (e.g. chlorpromazine). These are effective in 60% of cases with more impact on positive symptoms. Supports role of DA again, but what about 40% who don’t respond? Lack of impact on negative symptoms hints at two separate syndromes

Biology and Schizophrenia Consistent evidence for abnormal brain functioning in S patients but no single factor identified. Two syndromes? One caused by DA activity & associated with +ve symptoms; other caused by brain degeneration & associated with –ve symptoms. Cause & effect issues everywhere Confounding effects of drug treatment

On the board…… Draw the strength and weaknesses of the dopamine hypothesis on the board. NO WORDS!

Examination question – evaluate Evaluate the explanation for schizophrenia you have given in (b)(i). (4 marks) As excess dopamine is only measured after onset it could be effect not cause/eq; However paranoia in drug users where dopamine levels are kept too high does support the role of dopamine/eq; Also effectiveness of drugs that reduce availability of dopamine supports its role as implicated in the disorder/eq; Though antipsychotic drugs reduce dopamine availability in a very short time the effect on symptoms takes several weeks to appear, suggesting other factors are involved/eq; PET scans in those who have had the disorder for many years show blocking of dopamine receptors by antipsychotic drugs does not match a reduction in symptoms/eq; The positive correlation between schizophrenia and dopamine is consistent and according to Seeman (2006) without exception/eq;

What could be done to make dopamine synapses less active?

TREATMENT FOR SCHIZOPHRENIA

Before the 1950s schizophrenia was considered untreatable and patients were interned in mental institutions

Over time there have been a variety of different methods to treat schizophrenia

Rosenhan & Seligman vividly explain the back wards of mental hospitals as ‘snake pits’, filled with inmates who were unreachable or mutely catatonic, or were wild with delusions and straitjacketed. Attempts to treat schizophrenia such as insulin shock, ECT and drugs had failed.

Introduction Psychological problems are both distressing and disruptive for the individual sufferer. So, there is an immediate need to alleviate these conditions through appropriate forms of therapy and/or treatment.

Treatment v Therapy Definition of Treatment: the medical or surgical management and care of a patient. Examples: Chemotherapy, prescription of medicines to cure/treat symptoms of a disease or disorder. Definition of Therapy: In the broadest sense, Therapy is a term that can be applied to any form of treatment for any illness or disorder. For example, antacid is a form of therapy for heartburn, rehabilitation is a form of therapy for addiction, and exercise is a form of therapy for obesity. As it relates to mental health and mental disorders, therapy is usually a general term used to reference the sessions held between a therapist and a patient. E.g. Cognitive Behavioural Therapy (CBT), Family Therapy, etc.

Chemotherapy Since 50s use of drugs to treat mental disorders is widespread Types of drugs fall into following categories Anti-anxiety Anti-depressant Anti-psychotic Anti-manic Stimulants They work to either increase or reduce the levels of neurotransmitters

Anti-psychotic drugs have provided a breakthrough in treating schizophrenia and remain the main form of treatment Provide a calming effect BUT Have little effect on Type 2 Have side effects ANTIPSYCHOTIC DRUGS

2. Clozapine: blocks less dopamine and blocks more serotonin. a. Reduces both positive and negative symptoms. b. Fewer side effects;. c. Problem: produces a potentially lethal blood disorder. 1.Phenothiazines: decreases dopamine activity. a.Reduces positive symptoms (hallucinations, delusions, etc.). b.Fails to reduce negative symptoms (flat affect, low motivation, etc.). c.Unpleasant side effects: dizziness, nausea, sexual impotence, tardive dyskinesia (involuntary facial movements), etc. d.May cause permanent biochemical changes reducing possible eventual full recovery.

The knowledge that Chlorpromazine improves symptoms of schizophrenia while blocking D2 receptors for Dopamine has led to the development of drugs that have similar pharmacological properties to chlorpromazine. The symptoms that are most responsive to these types of drugs came to be called ‘positive’ symptoms because they showed a positive response to drug therapy.

Dopamine / serotonin pathways in the brain

DISCOVERY 1. In mid 1950s discovered that large daily doses of Amphetamines could produce a psychosis identical to schizophrenia Amphetamine increases D2 transmission 2. Chlorpromazine improves symptoms of schizophrenia Prevents Dopamine from activating

Antipsychotic medication Neuroleptics (e.g. chlorpromazine) bind to DA receptors without activating them

Dopamine antogonist CSjQ

Effectiveness Older (typical) drugs (e.g. chlorpromazine) Short term beneficial effect in 75% of patients (Davis et al, 1989) Long term beneficial effect in 55-60% (Davis et al, 1993) Most effective against positive symptoms High risk of side effects

Side effects Extrapyramidal side effects (EPS) Parkinson’s-type symptoms Postural & motor abnormalities Other side effects Sedation Weight gain Seizures

What implications arise from the side effects of antipsychotic drugs?

Effectiveness Newer (atypical) drugs (e.g. clozapine) As effective as typical drugs on positive symptoms; better for negative symptoms (Bilder et al, 2002) More effective with treatment-resistant patients (DeNayer et al, 2003) Less risk of EPS, but other side effects may occur (e.g. blood disorders)

Meltzer et al. (2004) P253 thick book.

Typical vs. atypical

PEE table (L for A*) PointExplainEvidenceEvaluateLink Schizophrenia is believed to be biological (dopamine Hyp)

Neo Neo