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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Psychological trauma exposure and posttraumatic stress disorder (PTSD) have been associated with advanced epigenetic age. However, whether epigenetic aging measured at the time of trauma predicts the subsequent development of PTSD outcomes is unknown. Moreover, the neural substrates underlying posttraumatic outcomes associated with epigenetic aging are unclear.
Methods
We examined a multi-ancestry cohort of women and men (n = 289) who presented to the emergency department (ED) after trauma. Blood DNA was collected at ED presentation, and EPIC DNA methylation arrays were used to assess four widely used metrics of epigenetic aging (HorvathAge, HannumAge, PhenoAge, and GrimAge). PTSD symptoms were evaluated longitudinally at the time of ED presentation and over the ensuing 6 months. Structural and functional neuroimaging was performed 2 weeks after trauma.
Results
After covariate adjustment and correction for multiple comparisons, advanced ED GrimAge predicted increased risk for 6-month probable PTSD diagnosis. Secondary analyses suggested that the prediction of PTSD by GrimAge was driven by worse trajectories for intrusive memories and nightmares. Advanced ED GrimAge was also associated with reduced volume of the whole amygdala and specific amygdala subregions, including the cortico-amygdaloid transition and the cortical and accessory basal nuclei.
Conclusions
Our findings shed new light on the relation between biological aging and trauma-related phenotypes, suggesting that GrimAge measured at the time of trauma predicts PTSD trajectories and is associated with relevant brain alterations. Furthering these findings has the potential to enhance early prevention and treatment of posttraumatic psychiatric sequelae.
The ongoing Eurozone crisis has brought to the fore the discourse of “austerity.” A number of countries, most dramatically Greece, have been called upon to institute policies of fiscal austerity as a condition of further support from the international financial community. The situation has generated some serious disagreements among economists, policymakers, and indeed important financial institutions such as the International Monetary Fund and the European Central Bank. Mark Blyth’s Austerity: The History of a Dangerous Idea speaks directly to these ongoing current debates. We have invited a range of political scientists working on related issues to comment on the book’s arguments and their relevance to the work that they do.
In his last press conference as chairman of the Federal Reserve's Board of Governors in 2013, Ben Bernanke was asked what advice he would offer Janet Yellen, the incoming chair, for dealing with Congress. Bernanke kept it simple: “Congress is our boss” (Federal Reserve 2013, 29). The Federal Reserve's (or Fed's) relationship with Congress is hardly that straightforward. Indeed, Bernanke immediately added: “It is important that we maintain our policy independence in order to be able to make decisions without short term political interference.” Bernanke's advice and admonition highlight the inevitable tension for Congress between insulating monetary policy from political pressure and holding the Fed accountable for its policy decisions.
The trade off between independence and democratic accountability is most apparent in the wake of financial and economic crises with interest rates at zero and central banks compelled to break the glass, tapping unconventional tools to ease policy further. Indeed, the recent global financial crisis reveals the limits of central bank independence. In the United States, Europe, and Japan, politicians have renewed their focus on central banks – replacing governors, revamping lending powers, and demanding greater accountability. Heightened oversight of monetary policy contrasts sharply with studies of central bank autonomy: Politicians are said to prefer independent central banks because more independent monetary authorities aim to deliver lower and more stable inflation (Alesina and Summers 1993). Committing in advance to central bank autonomy in theory prevents politicians from interfering with monetary policy to ease conditions for electoral gain.
Why and when do politicians threaten to revise the degree of independence they afford their central banks? And how does the current state of partisan polarization – coincident with the worst financial crisis since the Great Depression – affect how lawmakers react to the Fed's implementation of monetary policy? In this chapter, we focus on Congress's relationship with the Federal Reserve in the postwar period. First, we offer a framework for understanding how lawmakers influence monetary policy given expectations of central bank independence. We argue that Congress and the president largely shape monetary policy indirectly: setting goals for the Fed, reforming Fed governance, and imposing greater transparency. Second, we explore the conditions under which lawmakers threaten to change the Fed's goals, governance, or accountability.
There is one unavoidable fact about legislating in a democratic system. No single person, faction, or interest can get everything it wants. Legislating inevitably means compromising, except in the rare circumstances when consensus is so strong that one dominant view can prevail with ease.
Robert Kaiser 2013, p. 174
Compromise may be the “unavoidable fact” about legislating in a democratic system. Yet, scholars have few systematic answers to this question: How do legislators “get to yes”? To put the question in language more familiar to students of politics: How do politicians with diverse, often-conflicting interests and policy preferences reach agreements on public policy in a legislative body of co-equals? In this chapter, we offer a perspective on deal making in the contemporary Congress, highlighting the impact of political and partisan considerations on lawmakers' abilities to secure policy agreements.
Negotiation in Congress is never solely about policy: politics and policy are always intertwined. Congressional negotiations thus differ from those in the private sector, in which actors seek to maximize benefits and minimize costs and the substantive terms of an offer are paramount. Congressional deal making occurs in a political context that shapes the willingness of party leaders and their “rank and file” to negotiate at all or to accept even favorable offers. Lawmakers must justify votes and policy compromises to their constituencies, whereas party leaders must attend to key groups in the party coalition and to the party's public image. Given the political context of congressional negotiations, we evaluate the tools and institutional arrangements that make deals in Congress more likely – emphasizing that conflicting incentives and interests place a premium on negotiating out of the public eye. We conclude with a broader assessment of the prospects for negotiation in a party-polarized Congress.
DISTRIBUTIVE VERSUS INTEGRATIVE MODELS OF NEGOTIATION IN CONGRESS
Negotiation theorists typically distinguish between distributive and integrative solutions to public problems (see Chapters 4 and 5). Distributive solutions involve zero-sum bargaining over extant benefits.
Nearly unique amongst the world's monetary bodies, the Federal Reserve defies description as a central bank. A century after its creation, the Fed retains a hybrid structure of a president-appointed, Senate-confirmed Washington board and twelve largely privately directed regional reserve banks—each of which remains moored in the cities originally selected in 1914. In this article we investigate the origins of the Federal Reserve System, focusing on the selection of the twelve reserve bank cities. In contrast to accounts that suggest politics played no role in the selection of the cities, we suggest that a range of political interests shaped Democrats' choices in designing the reserve system. The result was a decentralized institution that initially proved unable to coordinate monetary policy—a key contributor to the onset of the Great Depression less than two decades later.
Minority Rights, Majority Rule seeks to explain a phenomenon evident to most observers of the US Congress. In the House of Representatives, majority parties rule and minorities are seldom able to influence national policy making. In the Senate, minorities quite often call the shots, empowered by the filibuster to frustrate the majority. Why did the two chambers develop such distinctive legislative styles? Conventional wisdom suggests that differences in the size and workload of the House and Senate led the two chambers to develop very different rules of procedure. Sarah Binder offers an alternative, partisan theory to explain the creation and suppression of minority rights, showing that contests between partisan coalitions have throughout congressional history altered the distribution of procedural rights. Most importantly, new majorities inherit procedural choices made in the past. This institutional dynamic has fuelled the power of partisan majorities in the House but stopped them in their tracks in the Senate.
Binder explores the history of rules changes in the U.S. House. She finds that majority parties typically change the rules to limit the power of legislative minorities for short-term partisan gain. Concerns about workload or institutional capacity have little effect on rules changes.
Compiling a manual of parliamentary practice in 1801, Thomas Jefferson emphatically recognized the importance of procedure in securing the rights of minority party members in the U.S. Congress. In a democratic political institution, majority parties would achieve their favored outcomes by taking advantage of their superior size, and minority parties would resist by availing themselves of protective rules to amend, delay, or obstruct the majority's agenda. Yet, the portrait of congressional rules as stable guarantors of the minority's right to participate meaningfully in the legislative process is deceptive. Far from rigidly securing the rights of the opposition, congressional rules are themselves the object of choice. Just as policy outcomes are contested by coalitions within each chamber, so too are the formal rules of the legislative game.
What leads members of Congress – in theory entitled to full and equal participation as members of a democratic legislature – to alter the procedural rights afforded members of the minority party? I shall articulate and test several competing explanations to account for formal changes in the rules of the House of Representatives that have created or suppressed minority rights from 1789 to 1990.
Binder explores the causes of legislative gridlock. Whereas previous scholars have concentrated primarily on divided party control between Congress and the president, Binder suggests that the distribution of policy preferences within Congress may play a more central role in causing gridlock. She finds that intrabranch party polarization and greater preference heterogeneity across the membership, as well as preference divergence between the chambers, lead to periods of decreased legislative productivity.
Although “gridlock” is said to have entered the political lexicon after the 1980 elections, stalemate is not a modern legislative invention. Indeed, in the very first Federalist, Alexander Hamilton complained about the “unequivocal experience of the inefficacy of the subsisting federal government” under the Articles of Confederation. Although stalemate may be endemic to American politics, no definitive account of its proportions or causes yet exists. In this article, I survey recent work, propose a new measure of gridlock, and test several alternative accounts of variation in gridlock over the last half-century.
There is no shortage of scholarship on the politics of gridlock. Most prominent is the work of Mayhew, who rejects the conventional wisdom that divided party control of Congress and the presidency dampens the legislative output of government. Subsequent work takes Mayhew as the point of departure, revisiting the questions he raised and researched. This project returns as well to Mayhew's work, probing in a new fashion the contours of gridlock in American national politics.
Chiou and Rothenberg raise important questions about how to measure key concepts in the study of legislative stalemate in the U.S. Congress. In challenging my choice of measures to capture bicameral differences, Chiou and Rothenberg argue that my findings are the artifact of measurement error. In this reply, I review the hurdles involved in measuring policy views over time and across institutions and suggest that the preferred measure of Chiou and Rothenberg falls short for measuring bicameral differences. Second, I assess the extent to which measurement choices affect the robustness of my findings about the determinants of gridlock. Drawing on new measures and model specifications, I show that my results are robust to alternative specifications. I conclude with an assessment of the broader challenges posed by how we measure critical concepts in the study of congressional performance.
Conflict within and beyond the United States Senate has refocused scholarly and public attention on “advice and consent,” the constitutional provision that governs the Senate's role in confirming presidential appointments. Despite intense and salient partisan and ideological disputes about the rules of the game that govern the Senate confirmation process for judicial appointees, reformers have had little success in limiting the ability of a minority to block contentious nominees. In this paper, we explore the Senate's brush with the so-called “nuclear option” that would eliminate filibusters of judicial nominees, and evaluate competing accounts of why the Senate appears to be so impervious to significant institutional reform. The past and present politics of the nuclear option, we conclude, have broad implications for how we construct theories of institutional change.Sarah A. Binder is Professor of Political Science at George Washington University and a Senior Fellow at The Brookings Institution (sbinder@brookings.edu). Anthony Madonna is a Ph.D. candidate at Washington University (ajmadonn@wustl.edu). Steven S. Smith is the Kate M. Gregg Professor of Social Sciences, Professor of Political Science, and Director of the Weidenbaum Center, Washington University (smith@wustl.edu). The authors thank Stanley Bach, Richard Baker, Greg Koger, Forrest Maltzman, Elizabeth Rybicki, Eric Schickler, and Greg Wawro for helpful comments and advice.
Perhaps the most striking feature of the Senate's practice of advice and consent today is the deference accorded home state senators in reviewing presidential appointments to the federal bench. Although the Constitution calls for the advice and consent of the Senate body, informal norms of the Senate provide home state senators with a potential veto of nominations to fill federal judgeships within their states. One norm—senatorial courtesy—historically ensured that senators would defer to the views of the home state senator from the president's party. Another practice—the Senate “blue slip”—allocates special procedural rights to both home state senators regardless of political party. A single objection from a home state senator from either party has historically been considered sufficient to defeat confirmation of a nominee. The blue slip also allows home state senators to influence the course of nominations prospectively—encouraging presidents to heed the preferences of home state senators in selecting new federal judges.