Movie clip: house (ao2 points …… ethics & side effects of biological model approach)
Biological explanationsof Schizophrenia
Assumptions of biologicalexplanations All mental disorders have a physical cause. (micro-organisms, genetics, biochemistry or neuroanatomy) 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.
Schizophrenia: geneticsfactorsPrevalence of schizophrenia is the same all overthe 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)
How do we study the influence Concordance rate:of genetic factors? the proportion of pairs where both If the concordance rate is individuals share a 100% in MZ twins it means certain characteristic. that the characteristic is genetically determined. If it less than the 100% but higher that DZ twins What does it mean? Twin However they However one studies might be is usually treated born bigger Dizygotic differently Monozygoticthan the other twins twins Share as Share the same many genes genes and the as siblings same but share environment the same environment
Family Adoption studies studiesChildren share 50% If the adopted childrenof their genes with have a higher each of their concordance rate for parents. If one of Sz with their biological their parent is parents than with their schizophrenic has adoptive parents, does the child more it support the chance to be influence of genetic schizophrenic? If factors? he/she is Sz, areonly genetic factors responsible?
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. The twin studies have all assumed that the shared environmental effects for MZ and DZ twins are equal which may be incorrect Twins are not representative of the wider population. (gestational environment) It is a very small sample. There are very few MZ twins in the population and only 1% are Sz. Are these diagnosis made using the same criteria?
Adoption studies Prevalence Prevalence amongst among biological adoptive relatives relativesKety et al 13% 2%(1968)schizophreniaonlyTienari et al 30% 15%(1994) all‘severe’ psych.diagnoses Could the psychiatrist making the diagnosis in the WereHowtheyweretheir biological theythatregularly? child Did influenced children when parents one offamily? Weretheyolddiagnosishe/she using the same adopted? be adopted by members of the were criteria? these see if made is aware extended both of the parents are Sz??
The overall picture This seems to indicate an influence of genetic factors but also the importance of environmental/ social factors
So have we found a generesponsible for Sz?In 2006, an Edinburgh University teamfound people carrying a variant of a genecalled neuregulin had a higher chance ofdeveloping psychotic symptoms. Howeversince then research has shown that Szinvolves a huge number of genes witheach of them making only a smallcontribution to the development of thedisorder according to Robin Murray aleading schizophrenia researcher.
Risk rises with degree of genetic relatedness Spouse – 1% (same as general population) Child – 13% DZ twin – 17% MZ twin – 48%Effect of shared environment?
Substantial evidence for a genetic contribution Some evidence disputed: Shared environment issues Diagnostic criteria in adoption studies All the evidence also suggests environmental triggers: Epigenetics could explain that the concordance rate is less than 100% in MZ twinsHeritability is similar with other major disorders such as breast cancer, hypertension, etc How is schizophrenia inherited and what exactly is inherited?
Schizophrenia: Biochemical The dysfunction of several neurotransmitter systems Dopamine, 5-hydroxytryptamine (5-HT; Serotonin) Glutamate are thought to play a part in schizophrenia. We will concentrate on the Dopamine Hypothesis
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
Lets remind ourselves howneurotransmitters work
DOPAMINE HYPOTHESISThe Dopamine hypothesis states that the brain of schizophrenic patients produces more dopamine than normal brains. –Evidence comes from –studies with drugs –post mortems –pet scans
Elevated Level of Normal Level of Dopamine In The Brain of a Dopamine In The Schizophrenic Patient Human Brain (specifically the D2 receptor) 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
Parkinson’s disease Parkinson’s sufferers have low levels of dopamine L-dopa raises DA activity People with Parkinsons develop schizophrenic symptoms if they take too much L-dopaChlorphromazine (given to schizophrenics) reducesthe symptoms by blocking D2 receptors
ROLE OF DRUGS–Amphetamines (agonists) lead to increasein DA levels–Large quantities lead to delusions andhallucinations–If drugs are given to schizophrenic patientstheir symptoms get worse
POST MORTEMFalkai 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 (left amygdala and caudate nucleus putamen) Concluded that DA production is abnormal for schizophrenia
PET SCANSLindstroem et al (1999) Radioactively labelled a chemical L- Dopa administered to 10 patients with schizophrenia and 10 with no diagnosis L-Dopa taken up quicker with schizophrenic patients Suggests they were producing more DA than the control group
Which Came First? The Chicken or the Egg? Schizophrenia or Faulty Chemicals? Faulty chemicals causeschizophrenia but schizophrenia may cause faulty chemicals Drugs may influence other systems that impact on schizophrenia so cant be 100% sure about their effects
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 when they begin to block dopamine immediately. We cannot seem to explain this time difference. It could be that the development of receptors in one part of the brain may inhibit the development in another. Type 1 cases respond well to conventional anti-psychotic drugs. Drugs such as CHLOPROMAZINE: Only effective at relieving the Positive Symptoms of the Illness. Not effective for negative symptoms. Therefore suggested that Type 2 is related to a different kind of abnormality such as brain structure. PET scans have suggested that drugs did not reduce symptoms of patients diagnosed with disorder for 10 yrs or more There may be other neurotransmitters involved. Possible that social and environmental factors trigger the condition.
Other possible causesBrain structureBrain damageViral infectionBirth complications
Brain structureSwayze (1990) reviewed 50studies of schizophrenics andfound that many had abnormallylarge amounts of liquid in thecavities of the brain. Suddath,who supports this found the sameenlarged cavities when using MRIscans on schizophrenic twins.
Structural abnormalities Unusually large corpus callosum High density of white matter in the right frontal and parietal lobe Small amount of grey matter in the temporal lobes A change in blood flow in the cerebral hemisphere MRI scan show unusually large ventricular enlargement but this is also seen in non- schizophrenics Hippocampus and the thalamus are all affected in the brains of schizophrenics
Brain Structure EvidenceAndreasen et 1990 – conducted a very well controlled CAT scan study and found significant enlargement of the ventricles in schizophrenics compared to controls.However this was only the case for men and not for women. Therefore can’t generalise the findings to women.
Brain StructurePeople withschizophrenia haveabnormally largeventricles in thebrain. Ventricles arefluid filled cavities.This means that thebrains ofschizophrenics arelighter than normal.
Enlarged ventricles due tomedications?Beng-Choon Ho (2010) However this was ain a longitudinal correlational study so itcorrelational study of does not show cause and211 schizophrenics found effect. Lewis’s study wasthat antipsychotic drugs carried out on animals sohave measurable we cannot extrapolate toinfluence on brain tissue humans without caution.loss over time. This wassupported by Lewis(2009) whoadministeredantipsychotic drugs toprimates and found abrain volume loss of10% .
FurthermoreIf the reduction inbrain volume is thecause of theschizophrenicsymptoms then itcannot explain whyafter 30 years of theinitial onset, 35% ofthe schizophrenics areclassified as "muchimproved“ becausethe cortex does notgrow back, if thestructural differenceswere the cause thenno improvementwould be possible.
Brain plasticityThe brain is aplastic organwhich changeswith the way weuse it so are thedifferences instructure thecause or the resultof schizophrenia?
Brain DamageDecreased rate of blinkingStaringLack of the blink reflex in response to a tap on the foreheadPoor visual pursuit movementsPoor pupil reactions to light
Viral InfectionIn recent years, there hasbeen a build up of evidencesupporting the role of viralinfections in the developmentof schizophrenia, including thepoliovirus, the flu virus and avirus called encephalitislethargica (inflammation ofthe brain that makes youtired‘).
Birth ComplicationsComplications during pregnancy,abnormal foetal growth andcomplications during delivery aresignificant risk factors in thedevelopment of schizophrenia.Those that play a significant role in thedevelopment of schizophrenia include:bleeding, diabetes and pre-eclampsiapregnancy complications
Birth Complicationsabnormal foetal growth and development problems including conditions such as low birth weight and reduced head circumferencecomplications of delivery including asphyxia (lack of oxygen) and emergency Caesarean sectionHowever, the effect of such complications is small in comparison with factors such as genetic pre-disposition to schizophrenia.