Neuroscience and Psychiatry 神経科学と精神医学

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Theodore Scott
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1 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

2 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

3 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

4 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.

5 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: Jones ME, Cockrum PC. A critical review of published economic modelling studies in depression. Pharmacoeconomics 2000; 17 (6):

Number of working days lost 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

6 Number of working days lost 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 Major depression Non-depressed 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:

7 Percentage of patients 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 No depressive symptoms (n=4,387) Acute depressive symptoms (n=652) Chronic depressive symptoms (n=501) * * 30 * 20 * 10 0 Absenteeism (missed work days) Presenteeism (decreased effectiveness) *p<0.001 vs no depressive symptoms Druss et al. Am J Psychiatry 2001;158:

8 Percentage of sample endorsing 50% or more of the time Productivity loss in a working cohort with MDD うつ病における仕事の生産性の低下 100 Moderately depressed (n=44) Severely depressed (n=37) Very severely depressed (n=25) Getting less work done Doing poor quality work Making more mistakes *Severity based on QIDS-SR score; MDD=major depressive disorder Lam. APA, 2009

9 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

10 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 Levels of inflammation-receptor proteins in blood vary with: sleep disturbance (Ryan et al. Circulation (2005) 112, ), body weight (Wellen & Hotamislioil Journal of Clinical Investigation (2003) 112, ), glycaemic state (Huerta & Nadler Current Diabetes Reports (2002) 2, ), diurnal variation (Miller et al. Brain Behaviour and Immunology (2003) 17, ), sample storage conditions (Flower et al. Cytokine (2000) 12, ).

11 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 HUMAN POSTMORTEM BRAIN TISSUE RNA

12 TUMOUR NECROSIS α: AN IMPORTANT INFLAMMATORY-RELATED PROTEIN (TNFα: 重要な炎症関連タンパク質 ) TNF α

13 TUMOUR NECROSIS α: FINDINGS IN BLOOD (TNFα: 血液における所見 ) (Mikova et al. 2001) Bipolar Disorder (Tuglu et al. 2003) (Fitzgerald et al. 2006) Major Depressive Disorder (Yang et al. 2007) (O'Brien et al. 2006) (Kim et al. 2007) (Pavon et al. 2006) (Penninx et al. 2003) (Kudoh et al. 2001) (Kim et al. 2007) (Lee et al. 2009) % Control Schizophrenia (Milaneschi et al. 2009) (Simon et al. 2008) (O'Brien et al. 2007) (Schlatter et al. 2001) (Brambilla et al. 2004) % Control (O'Brien et al. 2008) (Kim et al. 2009) (Erbagci et al. 2001) % Control

14 TUMOUR NECROSIS α: BIOLOGY (TNFαの分子経路 ) tmtnf stnf ADAM 17 stnfr2 stnfr1 ADAM17 TNFR1 TNFR2

15 TUMOUR NECROSIS α: BIOLOGY (TNFαの分子経路 )

TUMOUR NECROSIS α IN PSYCHIATRIC DISORDERS (TNFα: 精神疾患における変化 ) MEASURE TNF α (mrna) MAJOR DEPRESSIVE DISORDERS No Change BIPOLAR DISORDERS No Change SCHIZOPHRENIA No Change tmtnf α stnf α + 458

16 TUMOUR NECROSIS α IN PSYCHIATRIC DISORDERS (TNFα: 精神疾患における変化 ) MEASURE TNF α (mrna) MAJOR DEPRESSIVE DISORDERS No Change BIPOLAR DISORDERS No Change SCHIZOPHRENIA No Change tmtnf α stnf α % No Change No Change No Change No Change No Change TNFR1 (mrna) TNFR2 (mrna) No Change 53 % No Change 71 % % No Change Dean B et al. (2010) Journal of Affective Disorders 120: Dean B et al. (In Press) Molecular Psychiatry (mp [pii]; /mp [doi])

17 TUMOUR NECROSIS α PSYCHIATRIC DISORDERS: POTENTIAL CONSEQUENCES (TNFα: 精神疾患では何が起きているのか) MAJOR DEPRESSIVE DISORDERS

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

18 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)

19 Genetic classification of Autism Spectrum 自閉症圏の遺伝的分類 Control Subjects Autism Subjects 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 autism score (Skafidas et al, imol Psych 2012)

20 Genetic classification of Autism Spectrum 自閉症圏の遺伝的分類 Parents of Autism Subjects Control Subjects Autism Subjects 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% autism score (Skafidas et al, Mol Psych 2012)

21 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

22 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

23 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

24 Meta-analysis > 100 outcome studies in schizophrenia in highincome 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 preillness level of functioning). Revealed a substantial rate of recovery Approx 20% complete recovery and 40% social recovery (which includes those who achieved complete recovery)

25 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

26 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

27 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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Neuroscience and Psychiatry 神 経 科 学 と 精 神 医 学

Neuroscience and Psychiatry 神経科学と精神医学