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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
The rapid development of international law post-World War II also coincided with greater reliance upon treaties as a source of international law. Treaties had always been recognised as a source of international law, and their status was confirmed in art 38 of the ICJ Statute. It was the development of the UN, with its emphasis upon international law and focus upon treaty-making as a means of not only peaceful resolution of disputes but also multilateral agreement between States on matters of common concern, that was the catalyst for a greater reliance upon treaties in the conduct of international relations. This chapter begins by examining the growth of treaty-making, before considering what a treaty is, including the nature of 'instruments of less than treaty status'. It then covers treaty negotiation, creation and entry into force; reservations, objections and declarations to treaties; and legal obligations arising once a treaty has entered into force. The chapter then turns to treaty interpretation, and then examines how treaties are voided or ended through invalidity, suspension or termination. The chapter concludes with a discussion of amendment and modification of treaties.
Law-making is not a straightforward process in international law. This chapter focuses on the various law-making processes and structures available for creating international law. It first considers the traditional sources of international law as set out in art 38(1) of the Statute of the International Court of Justice generally and the concept of hierarchy of norms and relative norms before considering each of the art 38(1) sources in turn. The chapter concludes by considering alternative sources of international law not covered by art 38(1): 'soft law' including that created by non-State actors, and the role of the UN in creating international law.
Human rights are commonly invoked by States and individuals alike. Most recently there has been a spate of cases with a State accusing another of acts of genocide. The Convention on the Prevention and Punishment of the Crime of Genocide (Genocide Convention) is the first human rights treaty which the General Assembly of the United Nations adopted in 1948. As an example, it gave South Africa the basis for accusing Israel of acts of genocide for their activities against Palestinians living in Gaza even though it had no immediate and direct interest in the situation. Since the Genocide Convention a host of other treaties have been adopted and ratified by States and the United Nations machinery for administering them is now complex and sophisticated, despite the traditional enforcement mechanisms that domestic lawyers are accustomed to having behind them.
This chapter considers how resort to the use of force is addressed in the UN Charter, with particular reference to self-defence, including collective self-defence, and anticipatory self-defence. The contemporary right of self-defence is also assessed in light of the rise and influence of non-State actors. United Nations-sanctioned use of force is considered, with particular reference to the mechanisms that exist in Chapter VII of the UN Charter. The use of force by invitation, humanitarian intervention and the 'responsibility to protect' are also considered.
Jurisdiction refers to the ability of a State to make and enforce its laws. While often related to sovereignty, and intrinsically linked to its territory, jurisdiction can exist without a connection to territory. Jurisdiction can be held to exist in a variety of contexts, depending on the location of events, the nationality of participants or the surrounding circumstances, and will also indicate whether a State may be able to undertake enforcement action to uphold its law. This chapter considers the nature of jurisdiction insofar as it affects persons, corporations, ships and aircraft. The different types of recognised international law jurisdiction are each assessed, including territorial jurisdiction, nationality jurisdiction, universal jurisdiction, the protective principle, and passive personality jurisdiction. Jurisdictional immunities as they apply to States, Heads of States, State officials and diplomats are also considered.
International trade law is a subset of public international law and consists of the rules governing trade between nations. Historically this area of law was primarily concerned with trade in goods, but now includes trade in services (effectively the cross-border supply and consumption of services) and trade in intellectual property. International trade law has relevance to other fields of international economic law, including investment law. However, the focus of this chapter is on trade law as conducted under the auspices of the World Trade Organization (WTO), an organisation that commenced on 1 January 1995. This chapter briefly introduces these concepts, and then explains the current structure of the WTO. It then covers the core disciplines of the General Agreement on Tariffs and Trade 1994 and the main exceptions to these disciplines, before turning to the safeguards, dumping and subsidies regimes. The chapter then introduces the two agreements that cover regulatory standards at the WTO, and finally provides an overview of the General Agreement on Trade in Services.
This chapter considers the various means and methods for the peaceful settlement of international disputes as envisaged under the UN Charter and associated mechanisms. The key provisions of the UN Charter are considered, followed by an assessment of various methods of dispute settlement: negotiation, enquiry, mediation and conciliation, arbitration and adjudication. Given its significance to international law, particular attention is given to the ICJ and its jurisdiction in contentious cases and to deliver advisory opinions. The relationship between the ICJ and the Security Council is assessed, as are trends in dispute settlement.
A central feature of the international legal system is that States are the predominant actors within the system and possess international legal personality. States are able to enter into legal relations with each other by way of treaties, possess certain international legal rights as bestowed under international law, and are capable of enforcing those legal rights in international litigation or of being the subject of a claim if they are derelict in meeting their international legal obligations. This raises two important issues. First, how are 'States' characterised and recognised under international law? Second, are States the only international actors that possess international legal personality? This chapter first consides the characteristics of statehood and the legal tests for recognition of a State. Next, the political and legal dimensions of recognition of a State are considered. This is followed by a focus on the international legal personality of non-State actors, including international organisations, individuals and transnational corporations. Finally, the related issues of peoples and their right to self-determination, and secession are considered.
International environmental law provides a useful example of a rapidly developing field of international law, and demonstrates some of the difficulties involved in resolving modern global problems within the traditional legal framework. The environment did not feature in the Charter of the United Nations and none of the constituent bodies of the United Nations was expressly given an environmental mandate. Since the 1960s, however, and reflecting a similar trend in Australian domestic law, we can trace a steady growth in international law concerned with environmental issues. Early developments primarily focussed on particular instances of harm, resulting in international agreements that deal with a single issue such as the prevention of one type of pollution or protection of a particular wildlife species. As truly global problems became apparent - for example, depletion of the ozone layer, and global warming - the international community has developed agreements that are broader and more strategic in their approach.
A number of factors must be considered when reflecting on State responsibility and they are assessed in this chapter. First, what constitutes an internationally wrongful act for which a State may be responsible? Second, what conduct may be attributed to the State? Third, what reparation must a State make in the event it is held responsible for a wrongful act? Fourth, what defences might be available to a State that would preclude a finding of wrongfulness? Related issues such as diplomatic protection, nationality of claims, and the exhaustion of local remedies are also considered in this chapter.