Neuroscience and Psychiatry 神 経 科 学 と 精 神 医 学
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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):
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 )
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
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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