Lecture 7: Antipsychotics and Schizophrenia – 25th October 2016
Overview:
Schizophrenia and clinical aspects (Walter 2004, in Ann Rev Psychol; Neale
& Davison, Abnormal Psychology 2007)
Chlorpromazine: Archetypal antipsychotic or neuroleptic, clinical efficacy
and side-effects (review: Kane & Cornell, 2010)
Dopamine hypothesis for schizophrenia.
Atypical antipsychotics clozapine and risperidone (Tandon, 2008)
Environmental stressors and protective drug effects.
Psychotherapy and how antipsychotics may facilitate therapy
Schizophrenia: General Introduction
Broad construct with many ‘types’ of disorder... also changeable over time
in that there is not a consistent presentation of characteristics…good and
bad days/weeks?… compare with the concept - “depression”. It is only a
label, not an actual ‘thing’. Two people both with the label of schizophrenia
may present with differences. A label that denotes a problem that presents
with specific types of symptoms.
Incidence: One percent. Similar rates across societies.
o McGrath et al. (2008): Ratio for males:females was 1.4:1, only slight
difference. Those with schizophrenia have a two-to-three fold
increased risk of dying. Compared with native-born individuals,
migrants have an increased incidence and prevalence of
, schizophrenia. Exposures related to urbanicity, economic status, and
latitude are also associated with various frequency measures. In
conclusion, the epidemiology of schizophrenia is characterized by
prominent variability and gradients.
Various genetic, biochemical, and neurological factors.
o Increased risk of diagnosis with a first degree relative. Plomin et al.
(2001): Lifetime risk is 1% in the general population, increases to 10-
17% if the individual has a first degree relative who has schizophrenia
and for monozygotic twins it is 46-48%.
o There are different neurochemical theories for schizophrenia but not
one can account for 100% of the cases of schizophrenia, e.g. some
suggest it is related to dopamine system, some suggest serotonin
system.
o Helsinki study– Flu epidemic, in early 1950s, did a retrospective
analysis and found increased incidence of infants that developed into
adults with schizophrenia, incidence peaked during time of flu
exposure, increased susceptibility of foetus to developing
schizophrenia. Maternal influenza during pregnancy is a controversial
risk factor for schizophrenia in the child. Mednick et al. (1988): In the
context of a Finnish birth cohort study, they tested the hypothesis
that viral infection during the latter two thirds of foetal development
would increase risk of adult schizophrenia. Those exposed to the viral
epidemic during their second trimester of fetal development were at
elevated risk of being admitted to a psychiatric hospital with a
diagnosis of schizophrenia. This was true for both males and females.
, The second-trimester effect was seen in the elevated proportion of
schizophrenics among those admitted to a psychiatric hospital and
also in higher rates of schizophrenia per 1000 live births in the city of
Helsinki. The study has several limitations: (1) We have no direct
evidence that the subjects actually suffered a viral infection. (2) The
psychiatric data were obtained only for subjects up to the age of 26
years, 56 days. (3) The determination of stage of gestation at time of
exposure to the epidemic is based on date of birth. The viral infection
might have occurred outside the official epidemic window; the infant
may have had a preterm or post-term delivery. However, these
limitations are not likely to enhance the findings that it led to an
increase in risk of schizophrenia, so could be that true incidence was
higher than recorded.
o From core book: In Schizophrenia there is a small but significant
increase in ventricular brain ratio as a result of an increase in the
volume of the CSF (cerebrospinal fluid) filled ventricles in the brain
decrease in cerebral cortical tissue (Mirsky and Duncan, 1986;
Roberts and Crow, 1987).
o Also from core: Meta analysis showed 6% decrease in the left
temporal lobe and 9.5% decrease in the right temporal love of
neocortex, 44% increase in volume of left lateral ventricle and 36%
increase in right lateral ventricle (Lawre, 1998)
o These signs are associated with cognitive impairment. Important to
note that these may not be causes but schizophrenia may be a
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