This document summarizes the current understanding of the neurobiology of schizophrenia from several perspectives. It discusses findings from other neurodegenerative diseases that may inform schizophrenia research. Schizophrenia involves subtle neurodevelopmental disorders and has heterogeneous symptoms. Imaging and post-mortem studies have found structural brain abnormalities. Genetic studies have identified several candidate genes but none demonstrate a direct causal relationship. Environmental factors during development also interact with genetic factors. Mouse models aim to further understand pathophysiological mechanisms like the role of dopamine and glutamate. Future research opportunities include integrating genetic and human brain findings to better model the disorder.

1. The Neurobiology of Schizophrenia
Reggae
Jedi

2. Learning from other areas of
Neurobiology
➲ Knowledge from the neurobiology of
complex diseases raises through variants of
degenerative diseases via chromosomal pathways
➲ Knowledge of genes may illustrate a
pathogenic pathway
➲ Commonalities are being seen with
knowledge of genetic pathways
➲ Mutations between diseases can be
illuminating
➲ Genetic changes could be neurotoxic or
alterations in dosage of genes.

3. Lessons from developmental
diseases
➲ Schizophrenia is often viewed as a subtle
disorder of neurodevelopment
➲ The subtle disorders of neurodevelopment
may hold clues to the etiology and
pathogenesis of Schizophrenia

4. Schizophrenia: Clinical features
and Therapeautics
➲ Schizophrenia has no one single symptom so is
not diagnosed by laboratory tests
➲ Negative symptoms relating to psychosis
symptoms e.g. hallucinations, delusions are the
commonly noticable with diminishing social
relationships
➲ Success of neurobiological investigation will be
related to understanding the
heterogeneity (multiple symptoms of
Schizophrenia
➲ The onset of Schizophrenia usually begins in the
2nd
and 3rd
decade of life but childhood
noticeability is common.

5. Clinical features: Endophenotypes
➲ Heterogeneity can be classified through
phenotypes which are quantifiable and
heritable that can reflect neurobiological
features
➲ Some Endophenotypes have been related
to Schizophrenia but haven't been noticed
in wide scale samples
➲ Imaging studies that reveal neuro-
anatanomic deficits have also been
proposed as phenotypes

6. Clinical Features -
Neuropsychology
➲ Subtle cognitive problems that remain stable throughout
onset of Schizophrenia have been stable.
➲ This has related these impairments to be related to
endophynotic relevant to genetic analysis
➲ Cognitive domains of; Processing speed,
Attention/Vigilence, Working Memory, Verbal
Learning/Memory, Visual Learning/Memory, Reasoning
and Problem Solving and Social Cognition related to
endophynes are to be used in a clinical battery to relate to
Endophynotic and genetic relationships
➲ There are working memory deficits related to dysfunction
of dorsolateral prefontal cortex. Behavioural strategies
have been known to help in this area.

7. Clinical features - Neuroimaging
➲ Advances in imaging technology has led
investigators to examine larger areas of the brain
➲ Common structural abnormalities in
Schizophrenia include enlargements of lateral and
third ventricular, medial and temporal lobe volume
reduction and frontal lobe volume reduction
amongst others
➲ Abnormal development in brain structures occur
later in the development cycle
➲ For a badly performed task by somebody with
Schizophrenia there is a region of the brain
affected
➲ White matter disorganisation in the brain regions may
be a reason for these

8. Neuropathology
➲ Cytoarchitectural anomalies in entorhinal
grey matter have been found if not usual
features of degeneration in people with
Schizophrenia, providing suggestive evidence
➲ Reductions in cortical neuropil have also been
noticed in Schizophrenia patients
➲ White matter abnormalities could be related to
myelination which could be fundamental to the
disease

9. Pharmacology
➲ Anti-psychotics are the most common
therapy although psycho-social methods are
also used.
➲ First generation anti-psychotics led to
neurological side effects
➲ Newer antipsychotics help by blocking
Serotonin 5HT2A receptors
➲ Antipsychotics work mainly on positive
symptoms leaving sufferers unemployed and
disabled

10. Pathophysiobiology
➲ The dopamine hypothesis is the most
common relationship.
➲ The role of glutamate that requires
therapies to regulate this has some benefit
➲ The role of GABA in Schizophrenia has
been noted but requires further
investigation

11. Mouse models of Pathogenesis
➲ Social interaction, prepulse inhibition, aggression
and locomotor activity have been notable in mice
studies due to over expression of D2 dopamine
receptors in the forebrain causing cognitive
changes
➲ Changes in these receptors lead to familiar
behaviours seen in patients with Schizophrenia

12. Genetic linkage findings and
association studies
➲ Numerous gene relationships due to
deletions in gene linkages have been
associated with Schizophrenia
➲ These linkage problems are related to
interruption of chromosomes for
neurological development
➲ These include Dysbindin, D Amino Acid
Oxidase Actovator and COMT amongst
others, yet all only have relationships to
symptoms not direct cause or correlation

13. DISC1 – Interrupted by a
Chromosome
➲ The gene has been noticed via
chromosomal translocation segregating with
schizophrenia, bipolar disorder and other
major mental illnesses
➲ Although the translocation has also been
found in other blood donors as well
➲ DISC1 has also been found to affect areas
related to depression in the brain as well

14. Etiology – Environmental
Interactions
➲ Environmental and Genetic etiologies are
known to interact in Schizophrenia
➲ These include virus, pre and neo-natal
infection affecting brain development and
other factors that affect brain development
during an individual's life
➲ Other factors involved include premature
birth, low birth weight, pre-eclampsia,
rhesus incompatability, resuscitation at
birth, emergency casarean delivery

15. Conclusions and Possible Future
Research
➲ The current genetic knowledge can be combined
with knowledge of human brain
➲ Mouse models analysis can lead towards studies
in human brain development
➲ DISC1's interaction with proteins had led to
altered expressions in Schizophrenia.
Mutated genes can be found through DISC1
analysis
➲ These can be related to etiologies by using
DISC1 as a guide to discovering more about
Schizophrenia

16. Goodbye All!
➲ I hope this was a useful presentation
➲ I hope there are new ideas on
Neurobiology that you discovered through
this