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Neuroscience and Psychiatry
神経科学と精神医学
Ian Paul Everall
Cato Professor and Head
Department of Psychiatry
University of Melbourne
North West Mental Health
The Talk 本日の話題
What are we trying to do - help people affected by
mental illness
Why is it so important?
Give some examples of current neuroscience activity
in the Department
some suggestions as to how things could change for
the future
Our Ultimate Aim is To return them to ‘health’
“Health is a state of complete physical, mental and social well-being and not
merely the absence of disease or infirmity”
World Health Organisation
Why is neuroscience
Important? 神経科学が、なぜ重要か?
The Society for Neuroscience states
In 2007, the World Health Organization estimated that neurological disorders
affect up to one billion people worldwide.
Neurological diseases makes up 11 percent of the world’s disease burden, not
including mental health and addiction disorders.
The cost of these diseases is high across the globe. For example, the European
Brain Council estimated in 2010 that neurological diseases in Europe alone cost
one trillion dollars a year.
Mental Illness Costs Society a Lot of Money
(精神疾患は社会に大きな負担を与えている)
For example the total cost of major depressive disorder Total cost = direct cost + indirect cost
• Direct costs
–UK > €534 million (£333 million) (Kind and Sorenson, 1993)
–US > €2,350 million ($2,100 million) (Jones, 2000)
• Indirect costs
–Morbidity and loss of productivity
(€11,190 million = $US 10 billion)
–Loss from increased mortality
(€4,700 million = $US 4.2 billion)
Kind P and Sorensen J. The costs of depression. Int Clin Psychopharmacol 1993; 7: 191–195
Jones ME, Cockrum PC. A critical review of published economic modelling studies in depression. Pharmacoeconomics 2000; 17 (6):
555–583
Depression heavily affects work productivity
(うつ病は仕事の生産性に大きな影響を与えている)
Number of work days lost by patients suffering from MDD compared to non-depressed subjects
DEPRES II (Depression Research in European Society II):
A patient survey of the symptoms, disability and current management of depression in the community.
Int Clin Psychopharmacol 1999; 14: 139–151
Nu
mb
er
of
wo
rkin
g d
ays l
os
t
Major depression
Non-depressed
Depression has a huge impact on workplace productivity
うつ病は職場の生産性に
重大な影響を与えている
Druss et al. Am J Psychiatry 2001;158:731–734 *p<0.001 vs no depressive symptoms
No depressive symptoms (n=4,387)
Acute depressive symptoms (n=652)
Chronic depressive symptoms (n=501)
*
*
*
*
0
10
20
30
40
50
Pe
rcen
tag
e o
f p
ati
en
ts
Absenteeism
(missed work days)
Presenteeism
(decreased effectiveness)
Productivity loss in a working cohort with MDD
うつ病における仕事の生産性の低下 P
erc
en
tag
e o
f sa
mp
le e
nd
ors
ing
50
% o
r m
ore
of
the t
ime
Doing poor
quality work
Making more
mistakes
Getting less
work done
Moderately
depressed (n=44)
Severely
depressed (n=37)
Very severely
depressed (n=25)
0
10
20
30
40
50
60
70
80
90
100
Lam. APA, 2009
*Severity based on QIDS-SR score;
MDD=major depressive disorder
Examples of what we are doing
in Melbourne メルボルン大学における
我々の研究活動の例
Dean et al. 2012, insights into molecular pathology
of schizophrenia, bipolar disorder and major
depressive disorder
Skafidas et al. 2012, diagnostic test for autism
spectrum disorder
Inflammation related Proteins:
Changed in Psychiatric Disorders 精神疾患における炎症関連タンパク質の変化
IRP STUDIED Major Depressive
Disorders
Bipolar Disorders Schizophrenia
20 32 36 7 6 4 1 10 10 5
Levels of inflammation-receptor proteins in blood vary with:
• sleep disturbance (Ryan et al. Circulation (2005) 112, 2660–2667),
• body weight (Wellen & Hotamislioil Journal of Clinical Investigation (2003) 112, 1785–1788),
• glycaemic state (Huerta & Nadler Current Diabetes Reports (2002) 2, 396–402),
• diurnal variation (Miller et al. Brain Behaviour and Immunology (2003) 17, 276–285),
• sample storage conditions (Flower et al. Cytokine (2000) 12, 1712–1716).
RNA HUMAN POSTMORTEM
BRAIN TISSUE
STUDIES ON THE HUMAN CNS TRANSCRIPTOME
死後脳を用いたトランスクリプトームの研究
Dean & Scarr
TNF α
TUMOUR NECROSIS α: AN IMPORTANT
INFLAMMATORY-RELATED PROTEIN
（TNFα:重要な炎症関連タンパク質）
-40 0 40 80 120
% Control
Major Depressive Disorder
-40 0 40 80 120
% Control
Bipolar Disorder
-40 0 40 80 120
% Control
Schizophrenia
(Mikova et al. 2001)
(Tuglu et al. 2003)
(Fitzgerald et al. 2006)
(Yang et al. 2007)
(Kim et al. 2007)
(Pavon et al. 2006)
(Penninx et al. 2003)
(Kudoh et al. 2001)
(Milaneschi et al. 2009)
(Simon et al. 2008)
(O'Brien et al. 2007)
(Schlatter et al. 2001)
(Brambilla et al. 2004)
(O'Brien et al. 2006)
(Kim et al. 2007)
(Lee et al. 2009)
(O'Brien et al. 2008)
(Kim et al. 2009)
(Erbagci et al. 2001)
TUMOUR NECROSIS α: FINDINGS IN BLOOD
（TNFα: 血液における所見）
tmTNF
TNFR1 TNFR2
ADAM17 sTNF sTNFR2
ADAM 17 sTNFR1
TUMOUR NECROSIS α: BIOLOGY
（TNFαの分子経路）
TUMOUR NECROSIS α: BIOLOGY（TNFαの分子経路）
MAJOR
DEPRESSIVE
DISORDERS
No Change
+ 458 %
No Change
No Change
53 %
BIPOLAR
DISORDERS
No Change
No Change
No Change
No Change
71 %
SCHIZOPHRENIA
No Change
No Change
No Change
+ 179 %
No Change
MEASURE
TNF α
(mRNA)
tmTNF α
sTNF α
TNFR1
(mRNA)
TNFR2
(mRNA)
Dean B et al. (2010) Journal of Affective Disorders 120: 245-248.
Dean B et al. (In Press) Molecular Psychiatry (mp201295
[pii];10.1038/mp.2012.95 [doi])
TUMOUR NECROSIS α IN PSYCHIATRIC DISORDERS
（TNFα：精神疾患における変化）
MAJOR DEPRESSIVE
DISORDERS
TUMOUR NECROSIS α PSYCHIATRIC DISORDERS:
POTENTIAL CONSEQUENCES
（TNFα: 精神疾患では何が起きているのか）
Diagnostic Classifier for Autism Spectrum
Disorder using SNPs (Single Nucleotide
Polymorphisms)
一塩基多型(SNP)による自閉症圏の診断分類
a SNP is a DNA sequence
variation that occurs when a
single nucleotide differs
within a population or
individual
2 sequenced DNA fragments
AAGCCTA & AAGCTTA differ
by a single nucleotide
allelic frequency various
between ethnic groups
DNA molecule 1 differs from DNA molecule 2 at a single
base-pair location (a C/T polymorphism)
Genetic classification of Autism Spectrum
自閉症圏の遺伝的分類
Autism Genome Research
Exchange (AGRE)
database (6,774
individuals (2,609 ASD)
distribution of autistic
and non-autistic
individuals based on
genetic classification
Classification accuracy of
85% using 237 SNPs.
this is the 1st time that we
have a diagnostic test
(Skafidas et al, iMol Psych 2012)
autism score
Autism Subjects Control Subjects
Genetic classification of Autism Spectrum
自閉症圏の遺伝的分類
distribution of autistic and non-autistic individuals based on genetic (SNP) classification
Classification accuracy for Central Europeans and Tuscans was >85% using 237 SNPs
accuracy in an independent sample was >74%
(Skafidas et al, Mol Psych 2012)
autism score
Autism Subjects Control Subjects
Parents of Autism Subjects
Does Neurosciene Benefit Society? 神経科学を社会に還元できるか？
I hope that the two examples indicate how we
can help patients
Relates molecular and cellular pathology with
clinical symptoms or disorder classification
Is there Recovery? 統合失調症は回復するか?
Our view of disorders such as schizophrenia
coloured by the original descriptions of Emil
Kraeplin and Eugene Bleuler who emphasized
the chronic nature of the disorder and poor
recovery
Burghozli Hospital Study - Manfred Bleuler: 53%
of all subject and 66% of first admissions had
recovered significantly
20% had recovered fully
Iowa 500 study (Tsuang and Winokur, 1975) -
46% with schizophrenia had either improved or
recovered
Meta-analysis > 100 outcome studies in schizophrenia in high-
income countries in the 20th century assessed whether
individuals had achieved ‘social recovery’ (economic and
residential independence and low social disruption) or ‘complete
recovery’ (loss of psychotic symptoms and return to the pre-
illness level of functioning).
Revealed a substantial rate of recovery
Approx 20% complete recovery and
40% social recovery (which includes those who achieved
complete recovery)
What about those Living with
Mental Health Issues? 精神疾患を抱えて生きることとは？
Not so interested in the diagnosis
While symptoms such as depressed mood,
hallucinations etc can be distressing
More interested in issues pertinent to the recovery
model of mental health
Their own level of functioning
Recovery Model (Warner, The
Psychiatrist 2010) 回復モデル
Social movement influencing mental health service development
It refers to the subjective experience of optimism about outcome from
psychosis,
to a belief in the value of the empowerment of people with mental illness,
and
to a focus on services in which decisions about treatment are taken
collaboratively with the user and which aim to find productive roles for
people with mental illness
So What Could we do
Better? 今後我々がすべきことは？
We could consider correlating our findings to issues that are important
to those living with mental illness
Have markers of everyday functioning:
employment
relationships
cognition
This will be challenging but may help us understand functional issues
that are important to everyday life
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