Neurodevelopmental Hypothesis for Schizophrenia

Di Forti et al 2007
Incorporates many different hypothesis/ explanations of schizophrenia
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disruption of brain development leads to?
prenatally or early in life underlies later emergence of psychosis in adulthood
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What is a two hit hypothesis?
Genetics and environment
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Are born with what?
genetic predisposition, which then interacts with other, environmental things, e.g. mum ill during pregnancy, traumatic birth
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This may manifest in early life as what?
subtle motor, cognitive and social deficits • This combined with some kind of social adversity and the genetic predisposition, e.g. traumaleads to social anxiety, depression etc
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This may interact with what?
drug abuse in adolescence which precipitates a dopamine dysregulation (Weinberger-schizophrenia positive symptoms caused by overactivity of dopamine in the midbrain which causes reduced dopamine levels in prefrontal regions of brain which causes NS
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REsults in
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Kety et al (2002)
- In normal people, eyes constantly moving and flow smoothly - Pps asked to track target that moved sinusioidally
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What could controls do?
- Controls could do this easily and smoothly - Eye tracking in schizo significantly more irregular
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What does this suggest?
- Suggests low gain pursuit with frequent catch up saccadic eye movements
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What happens during low gain pursuit?
with frequent catch up saccadic eye movements
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During eye tracking use areas in pre frontal cortex?
this supports the hypothesis as those with schizo have deficits in this area, this area also linked with reduced dopamine so shows how different explanations link together
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Hippocampal cell changes
- This area crucial for normal brain function, especially for the encoding and retrieval of multimodal sensory information
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Conrad, Adebe and Austin (1991)
control pps cells are in an organised manner, in those with schizo are very disorganised
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Is also smaller what?
Smaller volume of hippocampus
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This is evidence that?
something occurred during development to cause these changes and therefore offers support for the hypothesis
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Could also explain some of what?
symptoms since deficits in this area disrupt processing of sensory information
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Prenatal experiences: Seasonality (Kendall and Adams, 1991)
more schizophrenics are born in February-May. A viral infection that obtained in the winter months may be accountable.
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What is this period?
This period also happens to be the second trimester -essential for the foetus’ brain development, so if a viral infection is present, this can hinder the development of the brain and result in many of the brain abnormalities seen in schizophrenics
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Venables (1996)
influenza associated with the cold months in Mauritius, correlated with an increased schizotypy score in the spring months. As study in Mauritius, those increased risk of schizo were born in September to December.
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Selten and Slaets (1994)
) tested if influenza in the second trimester was a risk factor for schizo in the child. Found there was no greater risk.
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Famine (St Clair et al 2005
was a famine in china between 1959-1961, meaning low nutrition to foetus, more schizophrenics born immediately after the famine.
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How does this support the neurodevelopmental hypothesis?
Supports bc shows how problem during development and that need interaction with genes since not everyone developed schizo
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Prenatal maternal infection is what?
risk factor for the development of the disorder
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Patterson (2009)
Animal models show that inducing infection in pregnant mothers (rats and mice) the offspring show behavioural abnormalities and neurochemical abnormalities that are reversed by antipsychotic drugs.
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When are cytokines released?
when immune system under attackand are contributors to normal development and function of the central nervous system
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So when mother has an infection during pregnancy what happens?
cytokines are released, these interact with environmental stressors to produce abnormal fetal processing of cells which causes abnormal behaviours in adulthood (Girgis et al., 2014)
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Zuckerman et al (2003)
Poly I:C used to mimic viral exposure because it elicits immune responses similar to those observed in viral infections
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Was injected inro pregnant rats, what was measured?
- Was injected into pregnant rats, baby rats were observed in terms of latent inhibition and dopamine release
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What was found?
- Found no difference between controls and experimental groups after 35 days, but after 90 days latent inhibition was disrupted (this could be reversed when rat was given antipsychotic drugs) and was increased dopamine release
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What is there evidence?
Immune system affects development as has consequences later in life
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Why is this study better?w
- This study is casual so good as all other studies are correlational
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Bilbo and Schwarz (2009)
they discuss how both infection prenatally and infection during early life leads to selective impairments in consolidation of memories that depend on hippocampus in adulthood and that early infection produces a latent/hidden change in the immune syst
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What is this consistent with?
the hypothesis which suggests combinationof early perinatal plus young-adult challenge (e.g., stress, infection) is required for the manifestation of the illness
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They looked at this by?
Injecting pregnant and newborn rats with ecoli
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Weinberger (1996)
neurodevelopmental hypothesis rarely criticised in the literature, main weakness is the clinical database on which it rests
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What did none propose?
links no direct evidence for the relationships, is circumstantial
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Weinberger also said a weakness was what?
hypothesis was difficult to disprove- lack of positive findings do not conclusively disprove it as subtle findings are easily missed.
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Physical anomalies eg
low set ears, two or more head holes etc. are indicators of schizo, however these can also be seen in other individuals- not a good measure
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However, what?
Rund (2018)review shows how most evidence suggest is no neurodegeration in schizo and states how those with the diseaseperform equally well in cognitive tasks as before the degeneration
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In conclusion
• Neurodevelopmental hypothesis has range of supporting evidence- suggests a good theory
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disruption of brain development leads to?


prenatally or early in life underlies later emergence of psychosis in adulthood

Card 3


What is a two hit hypothesis?


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Card 4


Are born with what?


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Card 5


This may manifest in early life as what?


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