Clinical Characteristics Profound disruption of cognition & emotion Affects language, thought, perception, affect and sense of self Symptoms typically divided into positive & negative

Positive Symptoms Reflect an excess or distortion of normal function: Delusions Experiences of control Auditory hallucinations Disordered thinking

Negative Symptoms Diminution or loss of normal function: Often persist during periods of few (or absent) positive symptoms Affective flattening Alogia -  poverty of speech Avolition – mistaken for disinterest

DSM-IVR Two or more positive symptoms must be present for a period of at least a month BUT Broad ‘validity’ issues with classification

Biological Approach to Abnormality: Causes of Abnormality Outline & evaluate Biological Approaches to SZ Biological Approach to Abnormality: Causes of Abnormality The biological model of abnormality assumes mental disorders as illnesses with a physical cause. The medical explanations of Schizophrenia are: Neuroanatomy (structure of brain) Brain biochemistry (function of brain) These may be the result of: Genetic factors Brain damage (infection or lesions)

Biological Explanations 1) Genetic factors 2) Biochemical factors (Neurotransmitters) 3) Neuroanatomical factors 4) Pregnancy & Birth Factors Comer (2003) – biological explanations have received most research support; therefore the more reliable and scientifically valid. Gottesman & Reilly (2003): biological ignores psychological; Diathesis-stress relationship may exist

1) Schizophrenia: GENETICS Gottesman (1991) Effect of genes or shared environment?

Genetic Factors I Family/Twin Studies Biological relatives of patient more likely to develop schizophrenia, and risk is greater the closer the relationship (Gottesman, 1991) Twin studies show that MZ twins have 48% risk of developing disorder (concordance) compared to 17% in DZ twins (Janicak et al., 2001) With strict diagnostic criteria, DZ = 0%, MZ = 26% (Cardno et al, 2002)

Genetic Factors II Adoption Studies Kety et al. (1998) found 14% of biological relatives of adoptees had disorder, compared with 2.7% of adoptive relatives Tienari (1991): compared 155 adoptees from Sz mother with matched group of non-SZ adoptees. 10% in ‘Sz mother’ group Vs 1% in ‘just adoptee’ group

Evaluation of Genetic Factors + Broad, strong research evidence (though there are issues: small samples, diagnostic criteria for inclusion  ‘more experimental control = lower concordance’) - Doesn’t account for patients with no close relatives with disorder (2/3 of those diagnosed) (Stirling & Hellewell, 1999) - High concordance rates in Family/Twin Studies may be due to similar rearing patterns (would be higher for MZ!) - Identical genes still only approximately 50% chance of disorder - Probably complex genetic contribution rather than ‘Sz gene’

2) Biochemical - The Dopamine Hypothesis Schizophrenia is caused by ‘excessive activity’ at synapses that use dopamine as their primary neurotransmitter (important roles in behaviour & cognition,  incl. mood, attention, working memory) More dopamine binding leads to increased ‘firing’ in the brain of DA-dependent processes This in turn causes abnormal functioning of DA-dependent brain systems, resulting in schizophrenic symptoms Evidence comes from: pet scans ; studies with drugs ; post mortems

How Neurotransmitters Work

PET SCANS BUT Crook et al (2000) – Scans not conclusive Typical Level of Dopamine in the Human Brain Elevated Level of Dopamine in Brain of a Sz Patient (specifically the D2 receptor) PET SCANS Neurons that use the transmitter ‘dopamine’ fire too often and transmit too many messages or too often. Certain D2 receptors are known to play a key role in guiding attention. Lowering DA activity helps remove the symptoms of schizophrenia BUT Crook et al (2000) – Scans not conclusive

Drug Studies 1) Amphetamines (agonists) lead to increase in DA levels: - Large quantities lead to delusions and hallucinations (i.e. induces SZ symptoms) - If given to Sz patients their symptoms get worse 2) Parkinson’s sufferers have low levels of DA: - L-dopa raises DA activity - People with Parkinson's develop SZ symptoms if they take too much L-dopa 3) Drugs which bind to D2 receptors, blocking transmission (e.g. Clozapine, given to SZs), alleviate major Sz symptoms BUT mostly positive symptoms - supports ‘Two Syndrome Hypothesis’ , Crow (1985)

Post Mortem Falkai et al (1988) Autopsies have found that people with schizophrenia have a larger than usual number of dopamine receptors. Increase of DA in brain structures and receptor density Concluded that DA production is abnormal for schizophrenia

Evaluation (Typical) Antipsychotic drugs only help positive symptoms (again, is SZ 2 syndromes then?) Newer (Atypical) drugs affecting other neuro- transmitters (eg. Serotonin) shown to be effective Cannot explain remission periods (takes up to 4 weeks to see any sign that the drugs are working when they begin to block dopamine immediately) Antipsychotics help with other disorders, not just SZ – so is SZ a disorder in its own right? Post mortem issues?

3) Neuroanatomical Factors Enlarged ventricles Cavities responsible for supplying nutrients & removing waste In patients, 15% bigger than normal (Torrey, 2002) Tendency for negative symptoms, greater cognitive disturbance & poorer response to traditional antipsychotics (Bornstein et al. 1992) Brain abnormalities Meyer-Lindenberg et al., (2002) – prefrontal cortex of patients showed reduced activation and DA levels were elevated Patients with ‘Type II’ schizophrenia also have smaller amounts of grey matter and smaller temporal & frontal lobes

Evaluation Supports view that enlarged ventricles significant only because they indicate reduced brain matter Further support to ‘2-syndrome’ hypothesis, Type I = ‘Acute’ = +ve symptoms = DA hypothesis Type II = ‘Chronic’ = -ve symptoms = neuroanatomy

4) Pregnancy & Birth Factors Viral infection during pregnancy: Virus dormant until puberty (Gherardelli et al., 2002) Significant number of patients born in winter (Torrey, 2000) Mothers of patients more likely to have been exposed to influenza virus (de Messias et al., 2001) MZ twin studies demonstrate fingerprint abnormalities in patient compared to normal twin. Fingerprints develop in second trimester – foetus most at risk of viruses (Comer 2003)

Evaluation + Can explain schizophrenia in patients without family history - Methodological problems – studies used correlational data, and some used DSM II (broader diagnostic range) - No evidence that all patients have been exposed to viruses MZ twins should have 100% concordance No clear thesis

Schizophrenia BIOLOGICAL Treatments L Schizophrenia BIOLOGICAL Treatments L.O: Describe and evaluate biological treatments of schizophrenia Framework: Construct a big picture from details / key features. Weigh evidence from different schools of thought.

Starter: How would the medical approach try to deal with Sz? What aspects of Sz will drugs NOT be able to engage with?

Biological Therapies Two main types of antipsychotics (a.k.a narcoleptics) – most common and ‘primary’ for patients with Sz: Typical antipsychotics - the first generation of antipsychotics (developed during the 1950’s) Atypical antipsychotics - a newer generation of antipsychotics (developed during the 1990’s) Plus - ElectroConvulsive Therapy (ECT)

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

Typical Antipsychotics e.g. Haloperidol, Chlorpromazine Antipsychotics block dopamine receptors (by occupying receptor space usually reserved for dopamine) – ‘dopamine antagonists’ Reduced or No Electric Message Electric Message

Typical Antipsychotics (T.A) Short term beneficial effect in 75% (Davis et al, 1989) Long term beneficial effect in 55-60% (Davis et al, 1993) Davis et al, 1991: review of 29 studies - higher relapse rate using placebo (55%) than T.A (19%) hostile and critical environment: relapse rate using T.A 53% vs. 92% placebo. supportive environment: relapse rate using T.A 12% vs. 15% placebo Most effective against positive symptoms High risk of side effects (e.g. 30% Tardive diskinesia)

Atypical Antipsychotic e.g. Clozapine These work differently from ‘typicals’ in that they only attach to the specific D2 dopamine receptors Also serotonin antagonists, but exact relationship unclear As effective on positive symptoms; better for negative symptoms (Bilder et al, 2002) More effective with treatment-resistant patients (DeNayer et al, 2003) Less risk of Extra Pyramidal Symptoms (t.d 5%), but other side effects may occur (e.g. blood disorders)

Mini-plenary Any other potential problems you can think of in using drugs alone to treat Sz?

ElectroConvulsive Therapy (ECT) There are 2 types, unilateral, bilateral Patients given muscle relaxant, anaesthetic and a small current for ½ a second to induce a seizure for 1min Patients usually receive 3-5 treatments Only measurably effective where symptoms of catatonia are present and in terms of treatment for drug-resistant catatonic Sz Common side effects include temporary short-term memory loss, confusion, paranoia, nausea, muscle aches and headache. Some people may have longer-lasting/permanent problems with memory/paranoia/depression.

ECT Efficacy American Psychiatric Association: The effectiveness of ECT was no different from that of medication Sarita et al, 1998: when using ECT on 36 Sz there was no difference vs placebo Adams et al, 2000: analysing 26 studies ECT was more effective than placebo in the short term but ... Drugs were better than ECT. ECT + drugs = most effective Tharyan F: Combining drugs and ECT only showed mild improvement in the ST, and only 1/5 patients benefited.