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Genomic variations underlying common behavior diseases and cognition trait in human populations

Final Report Summary - ADAMS (Genomic variations underlying common behavior diseases and cognition trait in human populations)

Executive Summary:

Neuropsychiatric diseases such as affective disorders, schizophrenia and addiction to alcohol are highly prevalent. According to the WHO (2002), they are among the top 10 leading causes of the global burden of disease for the age group 15-44. In elderly individuals, Alzheimer's disease is the most common cause of dementia and the fourth leading cause of death. Therefore, the search for the aetiological factors of these disorders is of utmost importance in future research Europe-wide. Once the underlying mechanisms are understood, causal and individually tailored therapies will become feasible.

ADAMS searched for and analyzed genomic variations underlying Alzheimer's disease (AD), alcoholism and schizophrenia. Though the genomic variations presumably associated with AD, alcoholism and schizophrenia were described in preliminary studies for European populations, the significance of the putatively associated alleles, genetic background as well as the role of environmental factors was poorly understood. ADAMS significantly extended the studies of genomic variations underlying these diseases by performing genome-wide association analysis (GWAS) in cohorts of patients and healthy individuals from several ethnic populations of Europe and Russia. Candidate regions, both newly found and reported previously for these diseases were additionally analyzed by sequencing.

Obviously, the multifaceted ADAMS project had at its core the application of GWAS methodologies, surrounded by various enabling and ancillary tasks. Both regarding scientific content (i.e. high-resolution human genetic studies and correlation with disease status) and regarding type of collaboration (i.e. collaboration between EU/AC countries and Russia), important ethics questions were identified and defined as core ADAMS objectives. To this end, particular emphasis was given on ethics and a separate work package was devoted to addressing following issues:

a) Regarding informed consent (IC) and research ethics committees ('RECs'), the REC approved IC documents vary considerably, with the standards applied by ADAMS beneficiaries and their local RECs being considerably simpler than the Seventh Framework Programme (FP7) EC standards.
b) There is a lack of appropriate norms covering scientifically valid use of an ethnic label to describe samples and data in genomics;
c) Although the transfer and sharing of genomics data and samples is an inherent part of the research conducted by international consortia, guidance that is clear and practical, yet protecting and respect individuals and communities, has yet to emerge;
d) Although it would often be advisable to conduct a community level interaction due to the intrinsic community / public health implications of genomics research, no agreed standard has been developed.

ADAMS is an example of emerging science leaping ahead of the development of appropriate international ethics support: many existing laws and guidelines were designed for research on persons, not biological samples and associated data, with reliance being placed on research ethics committees ('RECs') in matters of ethics and governance. ADAMS is also precisely the kind of innovative research that the EC strives to support. ADAMS has concluded that the reaction to this situation should include the following:

a) Until international applicable ethics and governance norms are formulated, a heightened responsibility must be shared between beneficiaries (in particular those from academia), and the EC in generating and applying provisional ethics processes and standards. (There is a need to build a foundation for this provisional guidance by developing a coherent and justifiable set of ethics principles and approaches. A contribution has been made by ADAMS to this end).
b) ADAMS has noted the influence that funders such as the EC have on ethics and governance of research, and concludes that funder responsibilities are twofold:
i) to support beneficiaries by providing provisional guidance for biological samples and data;
ii) to use their influence and recommend that information be provided in funding submissions on applicants will deal with the issues listed above;
c) RECs, beneficiaries and funders should be guided by the principles of openness and transparency so that problems are acknowledged and openly discussed as a step in moving forward towards good practices being internationally agreed.

Project Context and Objectives:

Neuropsychiatric diseases such as affective disorders, schizophrenia and addiction to alcohol are highly prevalent. According to the WHO (2002), they are among the top 10 leading causes of the global burden of disease for the age group 15-44. In elderly individuals, Alzheimer's disease is the most common cause of dementia and the fourth leading cause of death. Therefore, the search for the aetiological factors of these disorders is of utmost importance in future research Europe-wide. Once the underlying mechanisms are understood, causal and individually tailored therapies will become feasible.

The goal of this project is two-fold:
1. To investigate the molecular genetic underpinnings of common neuropsychiatric diseases in diverse European populations.
2. ADAMS is an example of emerging science leaping ahead of the development of appropriate international ethics support: many existing laws and guidelines were designed for research on persons, not biological samples and associated data, with reliance being placed on research ethics committees ('RECs') in matters of ethics and governance. ADAMS is also precisely the kind of innovative research that the EC strives to support.

Ad 1:

We are focusing on such genetically complex and multifactorial diseases as Alzheimer's disease, schizophrenia, and alcoholism, because:
i) they are common in adolescent, middle aged or elderly populations in EU/AC countries and Russia,
ii) they represent major burdens to the patients, their relatives and the respective communities, and iii) they are genetically complex and thereby amenable to large-scale genetic association studies, which gives the different participants the opportunity to focus on specific diseases, to share information and to use the cutting-edge techniques for the analysis of their sample collections available within the consortium. A profound knowledge of physiological neuronal processes and functions is a prerequisite for the understanding of neuronal dysfunction and a key to the development of better diagnostic means and treatments for neuropsychiatric diseases. Therefore, we are also investigating the molecular genetic underpinnings of physiological, unimpaired human episodic and working memory, because both capacities are heritable neurophysiological phenotypes closely related to Alzheimer's disease and schizophrenia, respectively.

Because genome-wide association studies (GWAS) have been shown to be a powerful approach to study genetics of common diseases, we apply high-throughput genomic technologies to study large series of clinically well- characterized individuals from ethnically heterogeneous populations in EU/AC countries and Russia.

Focus on Alzheimer's Disease (AD). AD is the most common cause of dementia and the fourth leading cause of death in middle-aged and elderly persons. We and others have shown that mutations in two homologous genes, presenilins (PS1 and PS2), are the major cause of familial and the most severe early onset AD (age at onset less than 65 years). Members of this consortium have also identified and studied additional mutations and polymorphisms related to increased risk for AD. ADAMS aims at identifying genes significantly and reliably associated with the risk for AD and at comparing the importance of the identified genetic factors in populations with distinct genetic background.

Focus on Alcoholism. Several lines of evidence support a role for genetic factors in alcohol dependence. Epidemiological studies reveal a two-fold increase of lifetime risk for alcoholism in close relatives of patients compared to controls. Classical twin studies demonstrated that heritability of alcoholism can be estimated as high as 48-73% in men and 51-65% in women. The concordance rate for alcoholism is twice as high in monozygotic as compared to dizygotic twins. Genetically determined alcohol preference has been demonstrated in experimental animals. Identification of the specific genes underlying alcohol dependence is a great challenge. Multiple genes with minor or modest genetic defects rather than single genes with major effects may contribute to alcohol dependence. ADAMS aims at identifying genes significantly and reliably associated with the risk for alcoholism and alcoholism-related behaviors and at comparing the importance of the identified genetic factors in populations with distinct genetic background.

Focus on Schizophrenia. Schizophrenia is a highly prevalent, chronic and devastating disorder with a high impact on the global burden of disease. Formal genetic studies have consistently documented the high heritability of this disorder. They have also shown that the respective vulnerability genes are likely to confer their effects in conjunction with environmental factors. It is probable that the genetic and environmental factors contributing to psychiatric disorders are heterogeneous, involving multiple susceptibility genes of modest effects and many rare variants with larger effects. The characterization of susceptibility genes will provide decisive insights into the pathophysiology of psychiatric disorders. While the progress of molecular genetic research into psychiatric disorders has been rapid (as reflected by the feasibility of conducting GWA studies and Whole Genome Sequencing) the availability of large and homogenously characterized patient and control samples with readily available phenotype information remains a difficult problem. ADAMS aims at identifying genes significantly and reliably associated with the risk for schizophrenia and schizophrenia-related behaviors and at comparing the importance of the identified genetic factors in populations with distinct genetic background.

Focus on disease-related cognitive phenotypes / QTLs. The idea underlying the endophenotype (intermediate phenotype) approach is that the genotype related to specific endophenotypes may be less complex than the genotype underlying the disease. Particularly valuable are endophenotypes, which change early in the disease process, even before the clinical diagnosis is feasible. With regard to schizophrenia and Alzheimers Disease, deviations in working memory and episodic memory are suitable endophenotypes, which have been shown to be sensitive to illness-related genes (like ApoE4). Genes that affect normal variation of episodic and working memory, and the speed of decline of these functions in the elderly, may therefore be strongly linked with the initial pathophysiology of these disorders. ADAMS aims at identifying novel gene variants for these quantitative cognitive traits, at examining the association of these QTL variants with illness-based phenotypes and at studying their effects on neuroimaging-related and CSF biomarkers.

Ad 2:

The multifaceted ADAMS project has at its core the application of GWAS methodologies, surrounded by various enabling and ancillary tasks. The main ethics issues are the following:

a) Regarding informed consent (IC) and research ethics committees ('RECs'), the REC approved IC documents vary considerably, with the standards applied by ADAMS beneficiaries and their local RECs being considerably simpler than the Seventh Framework Programme (FP7) EC standards. This is problematic as the ADAMS Grant Agreement requires that all beneficiaries comply with applicable EU law and Seventh Framework Programme (FP7) specific programs. Furthermore, neither the IC documents in use nor the EC standards are fully appropriate for genomics. Thus there are limits to the sufficiency of the EU guidance and the assurance given by obtaining REC approval that individuals and communities in genomics research will be respected and protected.
b) There is a lack of appropriate norms covering scientifically valid use of an ethnic label to describe samples and data in genomics;
c) Although the transfer and sharing of genomics data and samples is an inherent part of the research conducted by international consortia, guidance that is clear and practical, yet protecting and respect individuals and communities, has yet to emerge;
d) Although it would often be advisable to conduct a community level interaction due to the intrinsic community / public health implications of genomics research, no agreed standard has been developed.

ADAMS is an example of emerging science leaping ahead of the development of appropriate international ethics support: many existing laws and guidelines were designed for research on persons, not biological samples and associated data, with reliance being placed on research ethics committees ('RECs') in matters of ethics and governance. ADAMS is also precisely the kind of innovative research that the EC strives to support. ADAMS has concluded that the reaction to this situation should include the following:

a) Until international applicable ethics and governance norms are formulated, a heightened responsibility must be shared between beneficiaries (in particular those from academia), and the EC in generating and applying provisional ethics processes and standards. (There is a need to build a foundation for this provisional guidance by developing a coherent and justifiable set of ethics principles and approaches. A contribution has been made by ADAMS WP7 to this end).
b) ADAMS has noted the influence that funders such as the EC have on ethics and governance of research, and concludes that funder responsibilities are twofold:
i) to support beneficiaries by providing provisional guidance for biological samples and data;
ii) to use their influence and recommend that information be provided in funding submissions on applicants will deal with the issues listed above;
c) RECs, beneficiaries and funders should be guided by the principles of openness and transparency so that problems are acknowledged and openly discussed as a step in moving forward towards good practices being internationally agreed.

In summary, the objectives of the present project are:

Objective 1. To identify susceptibility genes for AD, alcoholism, and schizophrenia in EU/AC and Russian populations.
Objective 2. To study the molecular genetic underpinnings of physiological, unimpaired human episodic and working memory, because both capacities are heritable neurophysiological phenotypes closely related to AD and schizophrenia, respectively.
Objective 3. To compare the frequency of the disease-associated alleles identified in EU/AC with the populations of the Russian Federation.
Objective 4. To integrate the consortium data and meta-analysis data in a synopsis report on common and/or ethnically specific variations associated with neuropsychiatric phenotypes in human populations.
Objective 5. To develop molecular-genetic instruments, which are potentially applicable for high-throughput screening of the disease susceptibility alleles in populations or clinical cohorts.
Objective 6. To establish a 'Good Ethical Practice' guide for this transfrontier cooperation.

Specification of Objective 6.

The formal goals were:

a. Gather the different consent forms and participant information sheets from the EU/AC countries and the Russian Federation (RF)
b. Identification and listing of the relevant ethical bodies in the different countries
c. Define the status of ethics environment in each partner state
d. Identification, clarification and comparison of the different relevant regulations and legislations
e. Report on ethical practice of the consortium's participants
f. Transposition of the regulatory environment in EU/AC and RF

Project Results:

WP1: Alzheimer's disease

Alzheimer's disease is a common, severe dementing disorder with a high heritability of up to 80%. Common and rare variants influence the risk of developing Alzheimer's disease and genetics has succeeded with large consortium work in assessing the risk conferred by genetic factors using large cohorts. We sought to identify new susceptibility loci for Alzheimer's disease.

These results were published in (most important publications shown):

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Schumann G, et al., Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7119-24.

Glucocorticoid receptor antagonism blocks ethanol-induced place preference learning in mice and attenuates dopamine D2 receptor adaptation in the frontal cortex. Rotter A, Biermann T, Amato D, Schumann G, Desrivieres S, Kornhuber J, Müller CP. Brain Res Bull. 2012 Aug 1;88(5):519-24.

Cocaine effects on mouse incentive-learning and human addiction are linked to alpha2 subunit-containing GABAA receptors. Dixon CI, Morris HV, Breen G, Desrivieres S, Jugurnauth S, Steiner RC, Vallada H, Guindalini C, Laranjeira R, Messas G, Rosahl TW, Atack JR, Peden DR, Belelli D, Lambert JJ, King SL, Schumann G, Stephens DN. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2289-94.

WP3: Schizophrenia

Schizophrenia is a common, severe mental disorder with a high heritability of up to 80%. Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria.

WP4: Memory

Human episodic and working memory are heritable and polygenic cognitive traits. A dysregulation of episodic and working memory capacity is closely linked to Alzheimer's disease and schizophrenia, respectively. Importantly, unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. To this end, we performed a dense genome-wide screen to identify episodic memory- and working memory-related gene variants, rather than focusing on hypothesis-driven SNPs only. This approach turned out to be particularly rewarding, as we were able to identify two genes related to episodic and working memory in young adults (CTNNBL1 and SCN2A, respectively), which exceeded genome-wide significance. In addition, we generated a comprehensive, genome-wide list of SNPs associated with episodic and working memory performance. This list is particularly important, as it can inform other gene hunting projects, as well as drug discovery programmes.

WP5: Development of molecular-genetics instruments for high-throuput screening of disease susceptibility alleles

Newly discovered SNP markers from genome-wide associations studies carried out by Russian and EU collaborators were included into a preliminary biochip. The biochip approach was applied for the analysis of association of selected SNPs with the risk of developing Alzheimer's disease, schizophrenia and alcoholism in the Russian population (residents of Moscow and the Volga-Ural and Siberian regions). Patients with AD, alcohol dependency and schizophrenia, and control subjects of Russian origin have been tested to validate the sensitivity and specificity of the biochip. The genotype data are in agreement with previously described associations in both Russian and other European origin populations.

WP7: Ethics

Preamble: Obviously, the multifaceted ADAMS project had at its core the application of GWAS methodologies, surrounded by various enabling and ancillary tasks. Both regarding scientific content (i.e. high-resolution human genetic studies and correlation with disease status) and regarding type of collaboration (i.e. collaboration between EU/AC countries and Russia), important ethics questions were identified and defined as core ADAMS objectives. To this end, particular emphasis was given on ethics and a separate work package was devoted to addressing ethics issues.

Ethics focuses not on what we do, but what we should do, to live a right, good and just life; it involves the reflection on the every-day moral orientation that guides our decisions and action; ethics reflection requires that we leave the purely personal level, and take the 'ethical point of view' of impartiality and selflessness. However following the European Commission (EC),'ethics' is seen as being synonymous with 'governance'. Thus an implicit element of a 'ethics in ADAMS is compliancy with laws, regulations and formal approval requirements as well as respecting ethics principles values and approaches.

WP7_1: International Cooperation Partner Country Russia

A key aspect of WP7 that has only been partly reflected by responding to the Deliverables is the opportunity that ADAMS has given to reflect on ethics in the Russian Federation. An historical, systemic approach has been taken to this work which is now summarized.

The research relationship EU-Russia and record of cooperation in the scientific sector has been largely defined by the political and economic sea-changes that have occurred throughout the 20th, and into the 21st Century, although co-operations in the research area is one field that can represent a 'win-win situation. ' The EU and Russia have in recent years undertaken a range of research activities and adopted in 2002 an Action Plan to enhance Science and Technology co-operation, creating a 'Common Research Space' based on common values and shared interests. 'Road Maps' were formulated, aimed at developing these spaces by capitalizing on the strong EU and Russian intellectual heritage and knowledge capital to inter alia promote, identify and adopt best practices.

Contemporary Russia is undergoing legal, economic, social, scientific, political and educational transitional processes as it moves away from the Soviet period towards an as yet unclear new identity, grappling with the inherited legal base that was established in the Soviet period of their history. An aim of many aspects of the Russian legislative is the approximation of Russian law with those of international forums such as the EU; the development of normative research documents in Russia take into account instruments such as the Declaration of Helsinki; indeed Russian specialists in bioethics have been involved in drafting of some international ethics and legal instruments.

Russia has in general an equal coverage of research governance issues in its legislation and 'soft' normative codes when compared to the EU. When comparing the status of norms between the EU and Russia, what is striking are the similarities. Some differences are nevertheless found although the variations are perhaps no greater than many found amongst EU member states. There are a few divergences that raise doubts if Russia will, by following its own norms and obtaining local ethics approvals, comply with FP7/EC standards. These include weaknesses regarding RECs (research ethics committees) and that genetics and genomics are poorly covered (although the same applies to some extent to Europe , ). Russian research ethics guidance overly focuses on clinical trials and responding to the requirements of foreign pharmaceutical investigators needing to secure approvals, with there being no procedures for the approval of other kinds of research projects. , A problem is also that the implementation of legal instruments (and possibly also non-binding soft instruments) in Russia is reported as being challenging. A gap is held as existing between what is written in the laws, and how or if they are implemented. Many legal requirements are seen as being unrealistic and unenforceable, with ensuring coherency in the range of laws and regulations also being an issue.

The FP7 guidance entitled 'Ethics in research and international cooperation' deals with special issues that can arise in developing and emerging countries, the latter being a term that can be applied to Russia. The guidance holds that such countries face a constantly changing variety of situations that can result in a particular vulnerability of study participants; a potential vulnerability of the local research team, and a possible vulnerability of the local Ethics Review Committee. In considering if these assertions are applicable to Russia, the premise is that a historical view on the Russian ethics and governance environment and should be taken. The timeline of the research ethics and genomics from 1917-201 reveals intriguing time-line disconnects including:

- In the same year – 1948 – of the United Nations Universal Declaration of Human Rights, the Soviet Union was under strict ideological control by Stalin, with genetics being officially declared a 'bourgeois pseudoscience', with scientists being imprisoned of they pursued Darwinist theories;
- In the same year - 1953 - that Francis H. C. Crick and James D. Watson discover the chemical structure of DNA, an article in the Soviet newspaper 'Pravda' (translation: the Truth) accused some of the nation's most prominent doctors – particularly Jews – of participating in a vast conspiracy to poison top Soviet leaders;
- In 1991, J. Craig Venter describes a fast new approach to gene discovery using Expressed Sequenced Tags; in the same year, Russia becomes independent as the Soviet Union collapses (thereafter the Commonwealth of Independent States CIS is founded).

Timeline of Historical Indicators of Ethics and Science Environment

1917 October - Bolsheviks overthrow provisional government of Alexander Kerensky, with workers and sailors capturing government buildings and the Winter Palace in St Petersburg, and eventually taking over Moscow.
1922 Russia becomes part of the Union of Soviet Socialist Republics, USSR(this Soviet era ends in 1991)
1924 Lenin dies
1928 First Five Year Plan: Stalin announced the beginning of state industrialization of the Soviet economy.
1943 Vavilov dies in prison after criticizing the non-Mendelian opinions of Lysenko
1946 Constitution of the World Health Organization
1947 Nuremberg Code
1948 Science in the Soviet Union was under strict ideological control by Stalin; genetics was officially declared a 'bourgeois pseudoscience'
1948 General Assembly of the United Nations Universal Declaration of Human Rights
1948 Lysenko again decries the 'capitalistic' works of Mendel and Darwin; denounces Mendelian genetics as 'reactionary and decadent'
1949 10 West European nations create the Council of Europe
1950 Schuman Declaration: proposal of the creation of a supranational European institution that would manage pooled coal and steel production (Belgium, France, Germany, Italy, Luxembourg and the Netherlands.)
1953 An article in Pravda accused some of the nation's most prominent doctors – particularly Jews – of participating in conspiracy to poison top Soviet leaders (later retracted in the same year after death of Stalin).
1953 Francis H. C. Crick and James D. Watson discover the chemical structure of DNA
1953 Stalin dies
1956 Khrushchev reads the "Secret Speech," On the Personality Cult and its Consequences, denouncing the actions of his predecessor Stalin.
1957 Treaty of Rome creates the European Economic Community (EEC)
1958 Khrushchev becomes Premier of the Soviet Union.
1964 Khrushchev' deposed
1964 Collapse of Lysenkoism (connected to the fall of Khrushchev )
1964 The World Medical Association Declaration of Helsinki recommendations to guide physicians in biomedical research involving human subjects.
1973 First European Union expansion: Denmark, Ireland and the United Kingdom join
1975 Asilomar Conference on Recombinant DNA leads to scientists issuing voluntary guidelines to ensure the safety of recombinant DNA technology.
1975 Helsinki Revision introduced independent research ethics committees
1979 The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research U.S.
1982 CIOMS/WHO Proposed International Ethical Guidelines for Biomedical Research Involving Human Subjects.
1986 The effort is launched to sequence the human genome
1986 Single European Act (treaty which provides the basis for reed-flow of trade across EU borders and thus creates the 'Single Market')
1989 Berlin Wall falls
1990 Reunification of Germany
1990 HGP, Human Genome Project founded
1991 J. Craig Venter describes a fast new approach to gene discovery using Expressed Sequenced Tags
1991 Russia becomes "independent" as the Soviet Union collapses; Commonwealth of Independent States founded
1991 International Guidelines Ethical Review of Epidemiological Studies CIOMS/WHO
1993 Single Market is completed with the 'four freedoms' of: movement of goods, services, people and money: 'Maastricht' Treaty on European Union. The name 'European Union' officially replaces 'European Community'.
1993 CIOMS / WHO International Ethical Guidelines for Biomedical Research Involving Human Subjects
1996 ICH Guidelines Good Clinical Practice issued
1997 EU Convention on Human Rights and Biomedicine Oviedo
1999 Soviet science system has increasing severe resource difficulties
2000 Human genome sequenced and assembled
2001 Publication of the human genome sequence
2002 Revision CIOMS / WHO International Ethical Guidelines for Biomedical Research Involving Human Subjects
2003 Close of HGP
2004 The US Union of Concerned Scientists claims that interference from Bush administration has hindered government scientist's research, resulting in flawed policy decisions.
2004 USA: A school authority issued policy that high school biology teachers teach intelligent design theory of evolution (a school of thought that suggests a supernatural 'designer' is involved) and read a statement that Darwin's theory of evolution is "not a fact".
2005 UNESCO Universal Declaration on Bioethics and Human Rights,
2006 Article 'Political Science' in the New Yorker magazine states that The Bush Administration persistently controlled speech and movements of US scientists.
2007 9th World Russian National Council Resolutions calling for the Russian federal government to 'include theology in the list of scholarly disciplines recognized by the State Commission for Academic Degrees and Titles and to preserve theology as an independent scholarly field. '
2007 Open letter to President Putin from Russian Academy of Sciences objecting that theology should occupy a place among scientific disciplines; ' scientific disciplines deal with facts, logic, and proofs, but not faith.'
2009 Revision: International Guidelines Ethical Review of Epidemiological Studies CIOMS/WHO
2010 US: Under President Obama, the White House released a Scientific Integrity Directive aiming at protecting government scientists from pressure, thus ensuring that government make fully informed decisions.

WP7_2: The Main Contents of the ADAMS Ethics and Governance Maze

It was commented above that the status quo of guidance in ADAMS is a maze comprising a number of 'gap' issues where either (a) no guidance exists; (b) guidance exists of doubtful appropriateness, or (c) the guidance available are (also) not coherent. The main issues in this maze located by conducting the WP7 Deliverables will now be outlined.

WP7_3: Role of Research Ethics Committees

Research ethics committees/ review boards etc. ('RECs') are widely given an important gatekeeper role of ensuring good practices, especially regarding the protection of research participants. A key issue that a competent review body should review regarding genomic studies is the extent to which the participants could be identified from their biological materials or associated personal data. When RECs review a proposal concerning human biological materials they must be satisfied that all involved understand what degree of identifiability the researchers are proposing. When RECs are asked to review proposals concerning the establishment or use of collections and population biobanks they should be satisfied that the proposal includes a satisfactory oversight mechanism and that the conditions governing access for research use of the samples are appropriate and transparent.

RECs have been the subject of criticism and debate regarding how they function, and whether they are able to function, , with the main interwoven issues and problems being the following:

- Subsidiarity issues
- Informed Consent and RECs as hindrance or as barrier to research
- Criticism inconsistency of REC decisions
- Lack of material resources
- Shortage of immaterial resources
- Lack of Harmonization

A few of the main problems disclosed in WP7 are now presented.

WP7_4: Informed Consent and Review Ethic Committees

It has been seen in ADAMS that the contents of informed consent documents drafted by institutions and approved by the appropriate national RECs varying considerably. There are differences between the standards applied by RECs and the local standards applied by the beneficiaries; the norms applied by the ADAMS RECs are all less onerous than those that set by the EC for application in FP7 funded projects. This is critical as the ADAMS Grant Agreement reads that all beneficiaries shall comply with all applicable EU / national legislation, and any relevant future legislation and the requirements of FP7 specific programs.

In addition to a shortage of guidelines covering genomics that could help them make well founded judgments, RECs are often under-resourced. Without doubting the integrity of REC members, the question thus arises of the limits to the sufficiency of REC approvals to respect and protect individuals and communities. It would seem that the role that RECs are given by default in especially (as yet) ungoverned research areas represent a problematic delegation of decision making responsibility.

WP7 suggests that what is needed is a coping strategy to deal with the situation; the idea is not to deny the need for REC approvals, but to be aware where weaknesses exist, and compensate if possible.

WP7_5: The Appropriate Treatment of 'Ethnic' Data in Genomics

Another issue is the lack of genomics appropriate normative guidelines on the appropriate treatment of data and samples that are given an 'ethnic' label: the current Data Protection Directive (DPD) aims to protect individual's rights regarding information and data. It holds that the processing of some categories of data are especially sensitive and require special protection. Member States are for instance required to prohibit the processing of personal data revealing racial or ethnic origin, political opinions philosophical beliefs, and the processing of data concerning health. However many international genomic projects make use of ethnic descriptors as selection criteria and/or variables, e.g. most famously HapMag and ADAMS. One condition held as allowing the processing and use of ethnic descriptors is if informed consent was given. However much genomics research involves taking historic samples/ data from existing biobanks; the consent given may not specifically grant consent to the use of data that reveals ethnic origin. Under some legislation, seeking REC approval in absence of clear consent may be an option. The question is then: how should a REC make a judgment call; based on what principles? In filing any submission to a REC, what facts and justificatory arguments should researchers offer? Another issue is whether some kind of community assent process should be referenced in the Directive and be compulsory if labels such as 'ethnic' are applied?

WP7_6: Issue Data Transfer and Sharing

The transfrontier ADAMS is a paradigmatic example of complex international –omics research, comprising EU Member states, an associated country, and an International Cooperation Partner Country Russia. An inherent aspect of -omic projects is the transfer of data (and occasionally samples) that results from genomic analysis (which can in and of itself be personally identifiable), and the transfer of data sets containing clinical, health -related, ancestry/place of origin and phenotype related individual and aggregated data. The governance questions regarding data transfer are complex and dynamic, with the issues surrounding the export of samples and data being a potential stumbling block in projects. The growing role of large biobanks and datasets, and the cost and time involved in their production, contributes to various stakeholders having considerable interests which drive discussions on the duty to share, or need to retain, data and materials. There are various sources of guidance to address questions that arise from such transfers on an international, EU, FP7 and national level. They include laws, regulations, codes, guidelines (coming from various disciplines) and ethical reflections and principles. The conditions under which transfers can be made include if the data subject have given their consent unambiguously to the proposed transfer (often a problem with historical samples), and if high standards are met by all involved countries/institutions regarding the level of security in place. One instrument to that can be used to bring clarity and to legitimate transfers is to make contractual arrangements in the form of a Material Transfer Agreement (MTA). A Material Transfer Agreement is a contract between two parties involved in a research project that specifies exactly the nature of work that is to be done on materials given by the one party to the other. MTAs can play an important role in addressing the concerns regarding ownership, long-term storage and sample re-use. It typically consists of the following information:

- The materials to be transferred;
- The exact work to be done on the materials;
- The conditions of storage of the materials, including for instance details on building access and security;
- The people that are to work with the samples, typically the heads of research groups and all the members of their group;
- The duration of the collaboration;
- An agreement about data sharing and collaboration in analysis.

WP7_7 Need for Community Level Interactions

The possible implications of genomics research for the community or population beyond the individual are widely reported, yet the repercussions and consequences have not been integrated into research guidelines. Genetic information is unique and distinguishes an individual from other individuals; it may also at the same time reveal information about and have implications for that individual's blood relatives (biological family) including those in succeeding and preceding generations, and can characterize a group of persons (that can be labeled 'ethnic communities'). Thus a new social group or community can be said to have come into existence – namely, the biological group that includes entities outside the family circle. Projects that involve DNA samples from various international or transcultural settings (especially if any local, ethnographic information be also collected) present a 'unique combination of ethical issues' that are however not fully covered by existing guidelines. Questions arise as to whether or not genetic data belong exclusively to the single, specific individual from whom they are collected and if informed consent of individual ethno- cultural community members can be adequate for authorizing research that can bring risks of stigmatization for the entire group.

WP7_8: Locating Norms and Principles for the Provisional Guidance

It has been asserted that no clear and appropriate ethics/governance 'blue print' for action exists for ADAMS, and that until this situation is remedied, work-in-progress, provisional ethics processes and standards must generated and applied in projects such as ADAMS. It is necessary to identify or develop a coherent and justifiable set of principles and approaches as foundation for this provisional guidance (and as a basis for the wider international, interdisciplinary discussion that needs to continue and come to conclusions).

An attempt to identify the sources of norms and principles that can be asserted as being appropriate for ADAMS must include looking at 'hard' laws and regulatory instruments and 'soft laws' and texts e.g. codes and guideline that specifically cover ethical questions.

A final source of norms and principles is the role that research funders increasingly play with there being various categories of funders who can exert ethics and governance influences on a project, one of which are funders who have a direct influence, such as the role of the EC in ADAMS. The influence takes place at various stages in the funding process: at the level of setting the ERA research strategy; how the strategy is reflected in the content of research calls, and finally that of the EC ethics screening and review processes.

The EC set certain ethics criteria – a form of 'funder conditionalities' that are the foundations of the screening and review process that is an integral part of research proposal evaluation procedure. An appreciation of the role of funders in setting practical ethics norms - a role that can be problematic - is one of the highlights of the WP7 findings. It led to the recommendation (see Deliverable 7.9. Good Practices) that the responsibility for coping with uncertainty and developing and performing research ethics good practices in projects such as ADAMS must be shared (a push-pull interaction) between beneficiaries and the EC regarding the ethics and governance of the research being funded.

WP7_9: Norms for Genomics Research Ethics: Learning from Russia and the CIS?

Although Russia often reports that international normative research ethics documents such as the Declaration of Helsinki are reference points when drafting their national documents, it is asserted that Russia /CIS countries also have an important contribution to make in the international ethics discourse. This is based on the premise that history has influenced in the past which principles are developed, and which are selected e.g. Nuremburg Trials, and continues to make a contribution, e.g. recent events such Chernobyl and 09/11.

This being the case, the conclusion is that the process of developing or applying ethical theories, principles or models should be open to analysis in the light of critically considering the influences of historical factors including economic, political, military, scientific events, and major moral traumas. This process should be an exchange between the 'East', 'west', 'north' and 'South. ' It is not proposed that any inference be made that historical facts justify normative conclusions; deriving an 'ought' from an 'is' must be avoided.

The particular political historical background surrounding science in Russia suggests that the developments in formulating normative research ethics in Russia (and CIS) deserve particular attention and may be of special value. WP7 ADAMS has located the 2010 CIS Declaration on the Principles of Science Activity, drafted with support of UNESCO. This Declaration was developed by conducted a survey with various experts representing the CIS national scientific communities The document contains interesting statements such as Article 6 that reads that “scientists have the right to choose particular scientific-research projects proceeding from their own evaluation of social, humanitarian and ecological significance of the project. The scientific community respects ethically justified decisions of scientists.”

WP7_10: Closing Remarks: the WP7 Ethics 'Good Practices' Recommendations

The good practices formulated for the final Deliverable are in many ways the iterative product of the whole process of working through the ADAMS WP7 Deliverables, and are therefore reproduced below to end this report. As preface to the Practices, a decision tree is now reproduced that suggest the steps to be followed in the event of uncertainty in an EC funded project on a point of ethics or governance:

Decision Tree for Beneficiaries in Developing Provisional Good Practices:
Potential Impact:
NOTE: This automatically generated document does not support correct visualization of text format, tables, figures, and footnotes. An appropriately formatted version of this report has been uploaded as an attached PDF.

The results of research conducted within the ADAMS project, many of them deriving from collaborations between various partners, have been reported to the scientific community in about 70 mostly high-impact, peer-reviewed journals and at high-profile international conferences. At many occasions the public was informed about the increasing societal and economic burden of neuropsychiatric diseases, partially due to the growing human life expectancy all over the world. Public awareness was created for the fact that the consequences of this development can only be averted by successful research efforts resulting in the development of reliable preventive and therapeutic interventions. Altogether, the ADAMS project contributes to achieving the Lisbon Agenda's goals of growth, competitiveness and employment not only by the scientific progress reached, but also by successfully combining the scattered European resources in our area of research which will certainly come to fruition only in the near future.

List of dissemination activities:
Type of activities Title Date/Period Place Type of audience Countries adressed
Lecture The Weizmann Lecture 28.11.2012 Zurich, Switzerland Civil Society CH, Israel
Lecture World Psychiatric Association Conference 30.11.2012 Athens, Greece Scientific community International
Presentation Congress of Trauma and Emergency Surgery 12-15.5.2012 Basel, Switzerland Scientific community International
Lecture Brain Awareness Week 11.18.3.2012 Basel, Switzerland Civil Society CH
Presentation International Society for Psychiatric Genetics Conference 16.10.2012 Hamburg, Germany Scientific Community International
Lecture Sino-Swiss Science and Technology Cooperation 22.06.2012 Zürich, Switzerland Scientific Community China, CH
Lecture German Society for Psychiatry Conference 24.11.2011 Berlin, Germany Scientific Community D
Lecture Academia Engelberg Conference 15.09.2011 Engelberg, Switzerland Civil Society, Scientific Community CH
Lecture Swiss Conference on Internal Medicine 12.5.2011 Lausanne, Switzerland Scientific Community CH
Presentation Rotary Club, Genes and Memory 10.06.2011 Zürich, Switzerland Civil Society CH
Lecture Psychiatry Lecture, Athens University, Genetics of human memory and memory-related diseases: Understanding complexity 13.04.2010 Athens, Greece Scientific Community GR
Presentation International Society for Psychiatric Genetics conference 5.10.2010 Athens, Greece Scientific Community International
Lecture German Society for Psychiatry Conference 27.11.2010 Berlin, Germany Scientific Community D
Lecture NGFN Symposium, Molecular genetic studies in cognition 26.06.2010 Bonn, Germany Scientific Community D
Lecture Dresden Spring School 17.-20.03.2010 Dresden, Germany Scientific Community International
Lecture Harvard Colloquium, Genetics of human memory and memory-related diseases: Understanding complexity 03.03.2010 Boston, USA Scientific Community USA
Lecture 5th Santorini Conference 30.9.2010 Santorini, Greece Scientific Community International
Lecture Honorary Lecture, University of Belgrade, Genetics of human memory: Understanding complexity 26.6.2009 Belgrade, Serbia Scientific Community Serbia
Lecture sesam summer school 7.9.2009 Basel, Switzerland Scientific Community International
Lecture German Society for Psychiatry Conference 27.11.2009 Berlin, Germany Scientific Community D
Lecture Social, Genetic and Developmental Psychiatry Centre Conference 06.01.2010 London Scientific community UK
Newsletter IMAGEN Newsletter 01.03.2010 Study participants (teenagers) and their parents UK
Presentation University of Camerino; ERASMUS Conference 12.-14.4.2010 Camerino, Italy Scientific community Italy
Presentation International Society for Behavioural Neuroscience Conference 2.-4.6.2010 Sardinia, Italy Scientific community International
Conference International Symposium on Bioinformatics Research and Applications 13.-16.9. 2010 Storrs, Connecticut, USA Scientific community International
Presentation X-AFAR Congress 27.-28.9.2010 Brescia, Italy Scientific community Italy
Symposium Congress on Alcoholism and Stress 03.-06.05.2011 Volterra, Italy Scientific community International
Symposium World Psychiatric Association Congress 18.-22.09.2011 Buenos Aires Scientific community International
Symposium World Health Summit 22.-26.10.2011 Berlin, Germany Scientific community International
Presidential Symposium German Society for Psychiatry Conference 23.-26.11.2011 Berlin, Germany Scientific community Germany
Symposium American College of Neuropsychopharmacology Conference 04.-08.12.2011 Hawaii, USA Scientific community International
Symposium Human Brain Mapping Conference 10.-14.06.2012 Beijing, China Scientific community International
Plenary lecture International Society for Biomedical Research on Alcoholism Conference 08.-12.09.2012 Sapporo, Japan Scientific community International
Presentation ECNP-Targeted Expert Meeting on Addiction 27-28.08.2010 Amsterdam, the Netherlands Scientific community International
Presentation The State Key Lab of Medical Genetics Meeting 09.2012 Changsha, China Scientific community China
Presentation University of Queensland Centre for Clinical Research Conference 09.2012 Brisbane Scientific community Australia
Presentation Queensland Brain Institute Conference 09.2012 Brisbane, Australia Scientific community Australia
Presentation Society for Neuroscience 40th Annual Meeting 13-17.11.2010 San Diego USA Scientific community International
Meeting ADAMS Consortium Meetings 2-8 October 2010 Athen Scientific community EU, Russia
Meeting ADAMS Consortium Meetings 30 March- 2 April 2011 Moskow Scientific community EU, Russia
Meeting ADAMS Consortium Meetings 25-29 June 2012 Basel Scientific community EU, Russia
Conference World Congress of Psychiatric Genetics 4-8 November 2009 San Diego Scientific community International
Conference
German Society for Psychiatry Conference 25-28 November 2009 Berlin Scientific community German
Conference Meeting of the National Genome Research Network 27 November 2009 Berlin Scientific community German
Conference 5th Biennial International Society for Affective Disorders Conference 16-19 April 2010 Vancouver Scientific community International
Conference World Congress of Psychiatric Genetics 3-7 October 2010 Athens Scientific community International
Conference German Society for Psychiatry Conference 23-28 November Berlin Scientific community German
Conference Meeting of the National Genome Research Network 25-27 November 2010 Berlin Scientific community German
Conference Imaging and Cognition Genetics Meeting 16-18 June 2011 Oslo Scientific community European
Conference ECNP 3-7 September 2011 Paris Scientific community European
Conference World Congress of Psychiatric Genetics 10 -14 September 2011 Washington DC Scientific community International
Conference World Psychiatry 2011: Our Heritage and Our Future 15-22 September 2011 Buenos Aires Scientific community International
Conference
Neuroscience Congress 26-28 September 2011 Bamako Scientific community African and international guests
Conference Meeting of the National Genome Research Network 23-68 September 2011 Berlin Scientific community German
Conference
German Society for Psychiatry Conference 23-26 November 2011 Berlin Scientific community German
Conference ISBD 12-16 March 2012 Istanbul Scientific community International
Conference
European Mathematical Genetics Meeting 12-13 April 2012 Göttingen Scientific community European
Conference
Hexagon Alliance 29-30 April 2012 Kyoto Scientific community German, Japanese
Presentation Alzheimer's Research open day 24 April 2010 Institute of Psychiatry Civil Society UK
Presentation Alzheimer's Research open day 2 April 2011 Institute of Psychiatry Civil Society UK
Poster Diabetes risk alleles are protective for Alzheimer's disease risk in APOE e4 carriers. 16 July 2011 AAICD meeting,
Paris Scientific community International
Lecture Resequencing of the complement gene pathway to identify rare variants that affect risk of Alzheimer's disease October 2011 International Congress of Human genetics, Montreal Scientific community International
Poster Resequencing of the complement gene pathway to identify rare variants that affect risk of Alzheimer's disease March 2011 Alzheimer's Research UK annual meeting, Leeds; UK Scientific community International
Lecture Depression in Alzheimer's disease -the role of life events, epigenetics and genetics March 2010 25th ADI Thessaloniki, Greece Scientific community International
Conference European Human Genetics Conference 2012 24 June 2012 Nuernberg, Germany Scientific Community International
Other

Dissemination, (Intellectual) Exploitation and Potential Impact for Future Researchers Utilization by the European Commsion (Ethics Units) of Know-How Generated by ADAMS . Aim: to support the EC and other FP7 funded projects Start 2011
On-going - Policy Makers,
Scientific community International
Other

Dissemination, (Intellectual) Exploitation and Potential Impact for Future Researchers Utilization by the European Commsion (Ethics Units) of Know-How Generated by ADAMS to support A Specoific FP7 Project Start 2011
On-going - Policy Makers,
Scientific community Central Asian and European populations, that includes in the consortium Kazakhstan and Uzbekistan.
Other

Dissemination, (Intellectual) Exploitation and Potential Impact for Future Researchers Informed Consent Check List Guidance for Genetics/Gernomics Research 2012 –
on going- - Policy Makers,
Scientific community International
Publication
Contribution to a book entitled „Reseach Ethics in Psychiatry”; case study ADAMS. On-going - Scientific community German speaking
Countries
Lecture
Teaching Research Ethics Using FP7 ADAMS Project as Example Spring 2011,

Spring 2012 Basel Switzerland Scientific community, (University students; PhD students) Switzerland
Conference
Conference Contribution:
Paradoxical Dimensions of Ethics in 'Personalised' Medicine: Necessity of The 'Public' to Achieve the 'Personal' June
2012

Switzerland


Scientific community International
Conference
EACME European Association of Centres of Medical Ethics (EACME)

Conference Contribution:
Ethical Issues of Psychiatric Research with Minors. June
2012

UK Scientific community International
Other ADAMS Know-How as Input for Regio-Basel, Public-Private-Societal Core-Facility Biobank Initiative 2011 –On
going Switzerland Policy Makers,
Scientific community Switzerland
Other: Building a Research Ethics Support Network ADAMS Spin-Off Research Ethics Project: Supporting Swiss submissions for EU funding meeting ethics requirements 2012 –
on-going Switzerland Policy Makers,
Scientific community Switzerland
Conference Conference at Vavilov Institute of General Genetics - Russian Academy of Sciences 30/03/2011 Moscow, Russia Scientific community (higher education, Research) Russia
Presentations Molecular genetic factors of Alzheimer's Disease, Alcoholism and Schizophrenia. 30/03/2011 Moscow, Russia Scientific community (higher education, Research) Russia

In addition to these dissemination activities, ADAMS produced significant know-how and expoitable foreground. Some examples:

- Know-how on logistics, organisation and PR of large scaled scientific studies
- A protocol for reliable deep-sequencing in specimens with very low DNA quantity
- A database for transcriptomes of high and low alcohol drinking/preferring rats
- A database and data analysis system for large phenotypic data
- An integrated bioinformatics pipeline for analysis of next generation sequencing data
- A database of rare complement associated variants
- Biological microchip with a set of primers for the analysis of genetic predisposition to Alzheimer's disease (Russian Federation patent application ?2011146851)
- Method of analysis for determining the genetic polymorphisms associated with schizophrenia and alcoholism, a set of primers and oligonucleotide biochip for its implementation (Russian Federation patent application ?2012118224)

Ethics-related Dissemination, Impact, Exploitation Activities: Past, Ongoing, Planned

1 Activity with Impact for EC Funded Research

- ADAMS colleague Dr. Nicola Stingelin has been invited by the EC Ethics Unit to act as both external ethics reviewer for FP7 project submissions, and to take part in a working party looking at European Commission ethics SOPs;

- The European Commission also recommended as one of the funding conditions that the FP7 'InterPregGen' project consortium appoint Dr. Stingelin to act as external ethics advisor. InterPregGen is a genetic study of pre-eclampsia in Central Asian and European populations, that includes in the consortium Kazakhstan and Uzbekistan.

2 FP7 'Product' for Dissemination: Informed Consent Check List Guidance Document

The aim of this Check-List is to indicate the issues that do or may arise in genomic research to help ensure that all appropriate matters applicable to a particular research project are covered in informed consent documentation prior to consent being sought. The sources used to draft this document are various international best practices consent documents, with special focus on those developed with genomic research in mind.

3 Local (Basel) Dissemination: Lectures Given (where material presented discussed ADAMS work)

- Research Ethics , Faculty of Psychology, University of Basel;

- PhD Colloquium, PhD Medical and Health Ethics, Medical Faculty, University of Basel; various presentations on research ethics (using ADAMS as example).

4 Conferences Contributions (that drew on ADAMS work)

4.1 Swiss Clinical Trial Organisation (SCTO) Symposium 2012, “Personalisierte Medizin in der klinischen Forschung.“ poster: „Paradoxical Dimensions of Ethics in 'Personalised' Medicine: Necessity of The 'Public' to Achieve the 'Personal'?”

4.2 EACME European Association of Centres of Medical Ethics (EACME) Annual Conference, September 2012, Bristol United Kingdom. Abstract accepted for presentation: Ethical Issues of Psychiatric Research with Minors. Authors:

Ioana E. Hiriscau; Nicola Stingelin; Stella Reiter-Theil (associated article in preparation).
Author affiliations: Clinical Ethics Support and Accompanying Research (CESAR), Psychiatric Clinics of the University Basel / Hospital Basel, IBMB, Switzerland.

5 Region Basel Impact and Dissemination Activity: Biobank Project

Public-Private-Societal Core-Facility Biobank Initiative.*

6 Planned International Dissemination, Impact, Exploitation Activity, Workshop Project:
Title: “Meeting the Challenges of International Emerging Science Research Consortiums: Swiss. Russian, European Reciprocal Development of Research Ethics and Governance Norms”

The Workshop* would focus on international research in innovative areas in the life science, especially genomics, based on and expanding the collaboration that has arisen from the FP7 ADAMS project between inter alia Switzerland (represented by the University of Basel) and Russia. The two needs that explain and justify the workshop are the following:

- A need exists to explore the appropriate approach to the ethics and governance issues arising in emerging, innovative science, as illustrated by ADAMS from (a) a theoretical and (b) a practical point of view;

- There is an interrelated need to explore how to support researchers in Switzerland, Russia (and the EU) in interpreting, meeting and developing the ethics criteria that are increasingly set by funding bodies such as those set in EU FP7 calls.

Following the agreement of the Swiss National Science Foundation to support the project, efforts are ongoing to raise the balance required. The participants will primarily be philosophers and scientists involved in genomics from Russia and Basel, including but not limited to ADAMS collaborators at both senior and PhD student levels.

7 Supporting EU Funded Research in Switzerland

The ADAMS experience and those made by the spin-off work as ethics expert in Brussels wit the Commission has led to a collaboration in the field of research ethics between the Rector's Office at the University of Basel, Euresearch (Swiss Guide to European Research and Innovation), driven by Nicola Stingelin with the aim of supporting and networking Swiss applicants and beneficiaries involved in EC Calls .*

8 Planned Research Ethics Project: 'Innovative, Strategically Important Interdisciplinary '-Omics' Research: Developing Research Ethics 'Best Practices'

An application for the funding of an ADAMS WP7 follow-up project has been made to the Research Foundation of the University of Basel.* The key points are as follows:

- Status Quo: there is a shortfall of clear and relevant ethics guidance for emerging innovative sciences, e.g. –interdisciplinary –omics research such as that conducted at the University of Basel.
- Premise: A consequence of is that the academic community has a heightened responsibility to locate and comply with work-in-progress best practices (within their respective sphere of activity, influence, and feasibility).

- Conclusion: the research question is therefore to locate the basis for developing best practice guidance.

- Action Resulting from Conclusion: draft best practice guidance.

- Methodology: conducting expert interviews, holding workshop with scientists

- Aims: supporting researchers who are engaged in innovative interdisciplinary research and supporting those who are applying for funding in reflecting the application of best practices in their proposals.

9 Book Project

An invitation was issued in August 2012 to Dr. Stingelin to participate in the book project: “Research Ethics in Psychiatry” by working on a chapter discussing the ADAMS research.
Project Leader: Prof. Hanfried Helmchen; chapter co-authors are the ADAMS participants Prof. Wolfgang Maier and Prof. Michael Wagner, Department of Psychiatry, University of Bonn.

* Details available on request from Nicola.stingelin@unibas.ch

List of Websites:

http://www.adams-consortium.eu