What do we need to know?

1. What do we need to know?

2. LEARNING OBJECTIVES • describe the role of genetics in schizophrenia • describe family, twin and adoption studies as a way of studying the role of genetics in schizophrenia • explain how family, twin and adoption studies support the genetic explanation of schizophrenia

3. True/False • 3% of the population suffer from schizophrenia • The word schizophrenia means ‘split mind’ • The DVM is used to diagnose schizophrenia • A delusion is a positive symptom • The symptoms must persist for one year in order to be diagnosed as schizophrenic • The flattening of emotion is a positive symptom

4. Biological V Psychological explanations On a post it note write down what you understand the nature nurture debate to be about Nature V Nurture

5. Biological explanations of Schizophrenia

6. Assumptions of biological explanations • All mental disorders have a physical cause. (micro-organisms, genetics, biochemistry or neuro-anatomy) • Mental illnesses can be described in terms of clusters of symptoms. • Symptoms can be identified, leading to the diagnosis of an illness. • Diagnosis leads to appropriate physical treatments.

7. Genetics • Individuals may inherit a predisposition to certain illnesses. These are carried on genes, through DNA, which pass from one generation to the next • PREDISPOSITION = Increased vulnerability to a particular disease based on genetic factors or the existence of certain underlying conditions not yet active or revealed.

8. Genetics • Every human has 46 chromosomes (DNA) divided into 23 pairs. • During reproduction, 23 chromosomes from mum and 23 chromosomes from dad are combined to make an embryo (cells before a baby)

9. Genetics • This is how we get our characteristics from both of our parents. • If a disorder is caused genetically then we would expect individuals who are closely related to be more likely to have it

10. Genetics • How do we measure this? • Concordance rate: measures how often two individuals who are closely related have the same disorder.

11. Schizophrenia: genetics factors Prevalence of schizophrenia is the same all over the world (about 1%) • Supports a biological view as prevalence does not vary with environment • However, there are variations within broad geographical areas (e.g. Torrey 2002 – found high rates of Sz in Ireland, 4% of the population, the incidence is also high in Croatia and Scandinavian countries but low in Spain and Italy and very low in some parts of Africa) Is this a problem of reliability in diagnosis or is it the influence of environmental factors ?

12. How do we study the influence of genetic factors? Concordance rate: the proportion of pairs where both individuals share a certain characteristic. If the concordance rate is 100% in MZ twins it means that the characteristic is genetically determined. If it less than the 100% but higher that DZ twins What does it mean? Twin studies However they might be treated differently However one is usually born bigger than the other Dizygotic twins Monozygotic twins Share as many genes as ordinary siblings but share the same environment Share the same genes and the same environment

13. SO -Dizygotic twins (non-identical twins) share similar characteristics, much like siblings. • Monozygotic twins (identical twins) are the result of an embryo viably splitting early on in development. They share almost exactly the same Chromosomal DNA.

14. Genetics • Twin Studies look at all types of twins: • Twins can be identical (monozygotic,MZ) or fraternal (dizygotic, DZ). • Best of all Psychologists like to study MZ twins who have been reared apart to see if they develop the same disorder • Why do you think that is?

15. Family studies Gottesman (1991) Adoption studies Tienari (2000) Adopted children have a higher concordance rate for Sz with their biological parents than with their adoptive parents, which supports the influence of genetic factors Children share 50% of their genes with each of their parents. If one of their parent is schizophrenic the child has a greater chance of being schizophrenic. If he/she is Sz, are only genetic factors responsible?

16. Twin studies • Gottesman and Shields Reviewed the results of 5 twin studies looking for concordance rates for schizophrenia. These studies looked at 210 MZ twins and 319 DZ twins • It was found that in MZ twins there was a concordance rate of 35-58% compared with dizygotic (DZ) twin rates that ranged from 9-26%. • They also found a concordance rate in MZ twins of 75-91% when the sample was restricted to the most severe form of schizophrenia. • The milder forms of schizophrenia had concordance rates of 17-33% suggesting that there may be greater genetic loading with severe forms of schizophrenia.

17. Joseph (2004) calculated that the pooled data for studies prior to 2001 show a concordance rate for MZ twins at 40% and Dz twins at 7%. • But the twin studies have all assumed that the shared environmental effects for MZ and DZ twins are equal which may be incorrect….and Twins are not representative of the wider population. It is a very small sample. There are very few MZ twins in the population and only 1% are Sz. We need to question if these diagnoses are made using the same criteria

18. Adoption studies Could the psychiatrist making the diagnosis in the child be influenced if he/she is aware that one of both of the parents are Sz?? Were they adopted by members of the extended family? Were these diagnosis made using the same criteria? Did they see their biological parents regularly? How old were children when they were adopted?

19. The overall picture

20. Diathesis-Stress Model This model explains Sz as a result of both genetic factors ("nature"), and life experiences ("nurture"). This model thus assumes that a disposition towards a certain disorder may result from a combination of one's genetics and life experiences. The term "diathesis" is used to refer to a genetic predisposition toward an abnormal or diseased condition. This theory suggests a mental illness like schizophrenia is produced by the interaction of a vulnerable hereditary predisposition along with precipitating events in the environment – like death of a loved one, becoming homeless, stress at work etc

21. Vulnerability • The greater the underlying vulnerability, the less stress is needed to trigger the disorder. Conversely, where there is a smaller genetic contribution greater life stress is required to produce the particular result. • Even so, someone with a diathesis towards a disorder does not necessarily mean they will ever develop the disorder. Both the diathesis and the stress are required for this to happen.

22. So have we found a gene responsible for Sz? In 2006, an Edinburgh University team found people carrying a variant of a gene called neuregulin had a higher chance of developing psychotic symptoms. However since then research has shown that Sz involves a huge number of genes with each of them making only a small contribution to the development of the disorder according to Robin Murray a leading schizophrenia researcher.

23. From twin, family and adoption studies we can conclude that risk rises with the degree of genetic relatedness • Spouse – 1% (same as general population) • Child – 13% • DZ twin – 17% • MZ twin – 48%

24. Evaluation • Twin studies may be flawed - there may be reasons other than genetic which explain the higher concordance rates in MZs. • Can you think what they are?

25. Environmental Effects • MZ twins tend to be treated much more similarly to each other than DZs do. Therefore parenting issues could be duplicated, or applied more completely to both children in the pair. Also, there may be more identity issues - a problem experienced by some schizophrenics - because MZs are treated more like one person.

26. Methodological Effects • In the past, diagnosis of the disease in twin pairs was carried out by psychiatrists who knew all about the study, including whether or not they were assessing MZs or DZs! • The solution is to carry out a b***d diagnosis. • When this is done, concordance rates drop for MZs • However, the difference is still significant….

27. Overall there is substantial evidence for a genetic contribution • However some evidence is disputed: • Shared environment issues • Diagnostic criteria in adoption studies (Joseph 2004) • Methodological issues • The evidence also suggests environmental triggers: Epigenetics could explain why the concordance rate is less than 100% in MZ twins. Heritability is similar to other major disorders such as breast cancer, hypertension, etc

28. Now, please plan it Discuss means describe and evaluate June 2013 Discuss biological explanations for schizophrenia. (8 marks + 16 marks) At the moment just plan what you would include in the answer based on the genetic explanation

29. From the examiner’s report The commonest explanations for schizophrenia were genetics, the dopamine hypothesis and neuroanatomy. Other appropriate explanations included the roles of other neurochemicals, viral links and evolutionary explanations. The evaluations of the explanations were of mixed quality. There was a general lack of focus on the extent to which the explanations described could explain the development of schizophrenia.

30. Do you remember how neurones work? https://www.youtube.com/watch?v=c5cab4hgmoE

31. DOPAMINE HYPOTHESIS

32. Schizophrenia: Biochemical The dysfunction of several neurotransmitter systems are thought to play a part in schizophrenia • Dopamine • 5-hydroxytryptamine (5-HT; Serotonin) • Glutamate We will concentrate on the Dopamine Hypothesis

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

34. Lets remind ourselves how neurotransmitters work

35. DOPAMINE HYPOTHESIS The Dopamine hypothesis states that the brains of schizophrenic patients produces more dopamine than normal brains. Sz are also thought to have high numbers of D2 receptors resulting in more dopamine binding and therefore more neurones firing Evidence comes from • studies with drugs • post mortems • pet scans

36. Elevated Levelof Dopamine In The Brain of a Schizophrenic Patient (specifically the D2 receptor) Normal Level of Dopamine In The Human Brain • Neurons that use the transmitter ‘dopamine’ fire too often • Certain D2 receptors are known to play a key role in guiding attention. – disturbances in this process may lead to problems relating to attention, perception and thought processes • EVIDENCE: Lowering dopamine activity helps remove the symptoms of schizophrenia

37. Evidence from Parkinson’s disease • Parkinson’s sufferers have low levels of dopamine • L-dopa raises DA activity • People with Parkinson's develop schizophrenic symptoms if they take too much L-dopa • EVIDENCE: • Chlorphromazine (given to schizophrenics) reduces the symptoms of Sz by blocking D2 receptors

38. ROLE OF DRUGS Amphetamines (agonists) lead to increases in dopamine levels Large quantities lead to delusions and hallucinations If amphetamines are given to schizophrenic patients their symptoms get worse

39. Randrup et al Rats given amphetamines developed schizophrenia type symptoms

40. Antipsychotic drugs Antipsychotic drugs block the activity of dopamine in the brain. By reducing stimulation of the dopamine system these drugs eliminate symptoms like hallucinations and delusions.

41. POST MORTEM evidence Falkai et al (1988) Autopsies have found that people with schizophrenia have a larger than usual number of dopamine receptors. Increased levels of dopamine have been found in certain brain structures - left amygdala and caudate nucleus putamen. They concluded that dopamine production is abnormal for schizophrenia

42. Evidence from PET SCANS Lindstroem et al (1999) • Radioactively labelled the chemical L-Dopa • This was then administered to 10 patients with schizophrenia and 10 with no diagnosis • The L-Dopa was taken up quicker in the brain of schizophrenic patients • This suggests they were producing more dopamine than the control group

43. Which Came First? The Chicken or the Egg? Schizophrenia or Faulty Chemicals? Faulty chemicals cause schizophrenia but schizophrenia may cause faulty chemicals Drugs may also influence other systems that impact on schizophrenia so we cannot be 100% sure about their effects 

44. EVALUATION • There is a lack of correspondence between taking the drugs and signs of clinical effectiveness. It takes 4 weeks to see any sign that the drugs are working even when they begin to block dopamine receptors immediately. • At present there is still no accepted explanation for this time difference.  Drugs such as CHLOPROMAZINE are only effective at relieving the Positive (type 1) Symptoms of the Illness.  They are not effective for negative symptoms. This may suggest that Type 2Sz is related to a different kind of abnormality such as brain structure.  PET scans have suggested that drugs do not reduce symptoms of patients diagnosed with Sz for 10 yrs or more

45. Post Mortem studies – contradictory evidence • As drugs block the dopamine receptors - the brain compensates by making more dopamine  • Post mortem studies reveal that patients who have taken antipsychotic drugs before they die have higher than normal levels of dopamine in their brain.

46. Evidence from neuro-imaging research • Neuro-imaging studies (like using PET scans) have not yet provided convincing evidence of altered dopamine activity in the brains of people with SZ (Copolov 2000)

47. Clearly there are other possible causes of Sz • Brain structure • Brain damage • Viral infection • Birth complications

49. Brain Structure People with schizophrenia have abnormally large ventricles in the brain. Ventricles are fluid filled cavities. This means that the brains of schizophrenics are lighter than normal.

50. Brain structure Swayze (1990) reviewed 50 studies of schizophrenics and found that many had abnormally large amounts of liquid in the cavities of the brain. This has been supported using MRI scans on schizophrenic twins.