Biological aspects,schizophrenia

1. BIOLOGICAL ASPECTS OF
SCHIZOPHRENIA
- BY Dr.SRIRAM.R

2. Genetic factors
Dopamine hypothesis and
other biochemical factors
Brain structure
Associated factors – Birth complications/Viral

3. Prevalence of schizophrenia is the same all
over the world (about 1%)
Supports a biological view as prevalence does not vary
with environment
There are variations within broad geographical
areas (e.g. Torrey 2002 – found high rates of Sz
in Ireland (4%)
Incidence is also high in Croatia and
Scandinavian countries, but low in Spain and
Italy and very low in some parts of Africa

5. Twin studies
Share the same genes and
the same environment
However one is usually
born bigger than the
other
Share as many genes as
siblings but share the
same environment
However they
might be
treated
differently

6. 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.
Cardno (2002) – showed concordance rate of 26.5%
MZ and 0% for DZ

7. Twins are not representative of the wider
population (gestational environment differs)
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?

8. This seems to
indicate an influence
of genetic factors but
also the importance
of environmental/
social factors

9. Milder forms of schizophrenia CR is 17-33% (greater
genetic loading with severe Sz)
The twin studies have all assumed that the shared
environmental effects for MZ and DZ twins are equal
which may be incorrect
The finding of a higher rate of schizophrenia among
the biological relatives of an adopted-away person who
develops schizophrenia, as compared to the adoptive,
nonbiological relatives who rear the patient, provides
further support to the genetic contribution in the
etiology of schizophrenia

10. GENETICS - ADOPTION STUDIES
Tienari – 155 adopted children –
whose biological mothers had
schizophrenia –they had a
concordance of 10% compared to 1%
in adopted children without
schizophrenic parents.
This is very strong evidence that
genetics are a risk factor for
schizophrenia

11. Age of the father has a direct correlation with
the development of schizophrenia.
In studies of schizophrenic patients with no
history of illness in either the maternal or
paternal line, it was found that those born from
fathers >60 years old were vulnerable to
developing the disorder
All the evidence also suggests environmental
triggers: Epigenetics could explain that the
concordance rate is less than 100% in MZ twins

13. Several genes appear to make a contribution
nine linkage sites: 1q, 5q, 6p, 6q, 8p, 10p, 13q,
15q, and 22q
Further analyses of these chromosomal sites
have led to the identification of specific
candidate genes, and the best current
candidates are alpha-7 nicotinic receptor, DISC
1, GRM 3, COMT, NRG 1, RGS 4, and G 72
Dystrobrevin (DTNBP1) and neureglin 1
NEGATIVE SYMPTOMS

14. DOPAMINE
HYPOTHESIS

15. The theory evolved from two observations.
First, the efficacy and the potency of DRAs are due to
antagonism of D2 receptors
Second, cocaine and amphetamine (increase dopamine) are
psychotomimetic
The basic theory does not elaborate on whether the
dopaminergic hyperactivity is due to
too much release of dopamine,
too many dopamine receptors,
hypersensitivity of the dopamine receptors to dopamine,
or a combination of these mechanisms
Mesocortical and Mesolimbic tracts are most often
implicated

16. Normal Level of
Dopamine In The
Human Brain
Elevated Level of Dopamine
In The Brain of a
Schizophrenic Patient
(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

17. 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

18. • Evidence comes from
– studies with drugs
– post mortems
– pet scans
Brain of schizophrenic patients
produces more dopamine than
normal brains

19. • Amphetamines and cocaine lead to increase in
DA levels
• Large quantities lead to delusions and
hallucinations
• If drugs are given to schizophrenic patients
their symptoms get worse
• Drugs which block dopamine
(Phenothiazines) also seem to reduce the
symptoms of schizophrenia

20. • 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 (left amygdala and caudate
nucleus, putamen)
Concluded that DA production is abnormal for
schizophrenia

21. • Lindstroem 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 vs controls
Suggests they were producing more DA than the
control group
• Increase in D2 receptors in the caudate nucleus
of drug-free patients with schizophrenia

23. Serotonin: Causes both +ve and –ve symptoms in Sz.
Clozapine dec. +ve symptoms and has robust Serotonin
antagonist activity
NE : Neuronal degeneration in NE system may account
for anhedonia. Akathisia in Schizoaffective disorder
was found to be associated with increased levels of
norepinephrine (Agronin and Maletta, 2006)
GABA : loss of GABAergic neurons in hippocampus-
>dec. GABA->inc. dopaminergic activity
Substance P and neurotensin causing altered
neuropeptide mechanisms

24. Decreased muscarinic and nicotinic receptors in the caudate-
putamen, hippocampus, and selected regions of the prefrontal
cortex may directly impact cognition. There is also decreased
muscarinic receptor in the STG responsible for auditory
hallucinations in Sz (up to 48 per cent less muscarinic receptors
in the STG of schizophrenia brains than in healthy brains)
Source - http://www.schizophreniaresearch.org.au/category/research-news/2006-research-news/

25. Glutamate has been implicated because
ingestion of phencyclidine, a glutamate
antagonist, produces an acute syndrome similar
to schizophrenia
The hypotheses proposed about glutamate
include those of hyperactivity, hypoactivity, and
glutamate-induced neuro- toxicity
Abnormally low levels of glutamate receptors
are found in postmortem brains of people
previously diagnosed with schizophrenia
(Konradi and Heckers, 2003)

26. The main problem with previous
studies is that it is not found in
all schizophrenics.
This has lead to further research
done by Crow in 1985.
He suggested two types of
schizophrenia with two biological
causes.

27. TwoSyndromeHypothesis -Crow1985
Type one - genetically inherited
associated with dopamine –
characterised by positive
symptoms.
Type Two – Neurodevelopmenal
disorder – to do with Brain
structure – characterised by
negative symptoms.

29. The loss of brain volume widely reported in
schizophrenic brains appears to result from
reduced density of the axons, dendrites, and
synapses that mediate associative functions of
the brain
One theory, based in part on the observation
that patients often develop schizophrenic
symptoms during adolescence, holds that
schizophrenia results from excessive pruning of
synapses during this phase of development.

30. Swayze (1990) reviewed 50 studies of schizophrenics
and found that many had abnormally large amounts
of liquid in the cavities of the brain.
Suddath, who supports this found the same enlarged
cavities when using MRI scans on schizophrenic twins.
Beng-Choon Ho (2010) in a longitudinal correlational
study of 211 schizophrenics found that antipsychotic
drugs have measurable influence on brain tissue loss
over time.
This was supported by Lewis (2009) who administered
antipsychotic drugs to primates and found a brain
volume loss of 10% .

31. Whether an active
pathological process is
continuing to evolve in
schizophrenia patients is
still uncertain. Some
studies indicate
progression, while others
do not.

32.  Andreasen 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
CANNOT generalise the findings to women.

33. • There is a reduced symmetry in several brain areas in
schizophrenia, including the temporal, frontal, and
occipital lobes.
• This reduced symmetry is believed by some
investigators to originate during fetal life and to be
indicative of a disruption in brain lateralization during
neurodevelopment.
• High density of white matter in the right frontal and
parietal lobe.
• Small amount of grey matter in the temporal lobes.

34. PM findings and MRI -> decrease in the size of the limbic system including
the amygdala, the hippocampus, and the parahippocampal gyrus
Hippocampus is small, functionally abnormal and has disorganised neurons
Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. Arch Gen Psychiatric. 1991;48:415

35. PM studies show anatomical abnormalities in
the PFC.
Functional deficits have also been
demonstrated.
It has long been noted that several symptoms of
schizophrenia mimic those found in persons
with prefrontal lobotomies or frontal lobe
syndromes.

36. Volume shrinkage or neuronal loss, in particular subnuclei
The medial dorsal nucleus of the thalamus, which has reciprocal connections with the prefrontal
cortex, has been reported to contain a reduced number of neurons
Number of neurons, oligodendrocytes, and astrocytes is reduced by 30 to 45 percent in
schizophrenic patients
Photomicrographs of Nissl-stained frontal sections through the
anterior (A), middle (B), and posterior (C) levels of the mediodorsal
nucleus

37. Many patients with schizophrenia show odd
movements, even in the absence of medication-
induced movement disorders
Examples are akathisia, facial grimacing, stereotypies
The movement disorders involving the basal ganglia
(e.g., Huntington's disease, Parkinson's disease) are the
ones most commonly associated with psychosis
Increase in the number of D2 receptors in the caudate,
the putamen, and the nucleus accumbens

38. Decreased rate of blinking
Staring
Lack of the blink reflex in response to a tap on
the forehead
Poor visual pursuit movements
Poor pupil reactions to light
Abnormal eye movements in 50 to 85 percent
of patients with schizophrenia

39. In recent years, there has been a build up of evidence
supporting the role of viral infections in the development of
schizophrenia, including the poliovirus, the flu virus and
encephalitis lethargica virus
Data supporting a viral hypothesis
increased number of physical anomalies at birth,
an increased rate of pregnancy and birth complications,
seasonality of birth consistent with viral infection,
geographical clusters of adult cases, and
seasonality of hospitalizations

40. Complications during pregnancy, abnormal foetal
growth and complications during delivery are
significant risk factors in the development of
schizophrenia.
Those that play a significant role in the
development of schizophrenia include: bleeding,
diabetes and pre-eclampsia.

41. Summary
Biological explanations do account
for schizophrenia, however the fact
that there is no conclusive
explanation that accounts for all
schizophrenics – psychological
explanations need to be
considered.

42. KAPLAN AND SADOCK SYNOPSIS OF PSYCHIATRY
www.schizophrenia.com
Various sources from the internet