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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The previous chapter showed that in mid-century England, where marriage loomed large as a political and moral topic, Richardson’s Anglican marriage plot elevated the novel form by figuring marriage as an institution joining the church and the state, and then by imagining characters like Pamela and Sir Charles Grandison who enact and embody that nexus. In the end, Richardson’s novels authorise their own imaginative – that is to say, literary – power by mediating between faith and citizenship (or better, by relaying faith into conjugality) inside the Erastian nation state.
It turns out, however, that the latent nation-building tendencies of Richardson’s marriage plots are more fully realised in a different programme: in a series of mid-century oppositional and satiric-sentimental novels that respond to Pamela. Of these, the most important are Fielding’s Joseph Andrews (1742), John Shebbeare’sThe Marriage Act (1754) and Oliver Goldsmith’s Vicar of Wakefield (1766).
This chapter outlines the theo-political conditions under which the English marriage plot was established. It shows how a particular party faction, the Court Whigs – which was committed both to a view of church-state relations that I call Erastian and to a particular understanding of natural law – reformed the regulation of marriage. Yet these efforts immediately met with contestation, much of which was based on alternative understandings of natural law and, implicitly, of church-state relations too. In the welter of debate triggered by the legislation, marriage was viewed as central not just to the polity but also to the divine order.
Clandestine marriage played a significant role in the English marriage plot’s development. Before being suppressed by the Marriage Act, it had spawned its own popular culture, whose history helps to explain what was at stake in the division of ‘proper’ from ‘improper’ ceremony that was so important to the new genre. This chapter outlines the conditions for the rise of clandestine marriage before taking account of its cultural profile centred on London’s so-called Fleet marriage market, a hub of the city’s boisterous commercial street life and tavern culture and a focus of its stage entertainments. If the marriage debate appealed to erudite theories in the halls of power, clandestine marriage and its representations belonged to more unruly and demotic spaces. In a remarkable feat of reconfiguration, however, by the century’s second half clandestine marriage had become an element of respectable (and sentimental) culture.
This study has made the case that the secularism of the English marriage plot has been too readily assumed. That assumption dissolves as soon as the genre’s early political contexts are more fully taken into account: Court Whig hegemony, the passage of and intense resistance to Hardwicke’s Marriage Act and the marriage debates that follow. Yet the origins of the English marriage plot are nothing if not layered. The novels of Richardson, Fielding, Shebbeare and Goldsmith shaped the genre and retain connections to improper marriage cultures. Old urban clandestine wedding markets and theatrical mock marriages continue to haunt them even as, promoting various Anglican and political interests, they invent a genre for which proper church ceremony is central.
Four city blocks south of where I write these sentences in Baltimore, a banner hangs on the façade of a famous Unitarian church. Taking a stand in the debate over same-sex marriage, it reads: ‘Civil marriage is a civil right.’
Frances Burney and Jane Austen both wrote their era’s definitive marriage plot novels, yet it is obvious that their heroine-centred courtship fiction stands at a distance from Fielding, Goldsmith and Shebbeare’s clerical and gentlemanly fictions – and even from Richardson’s Pamela. Most strikingly, proper ceremony holds no interest for Austen and Burney. In their novels conjugal attachment does not express Anglican piety or natural law; rather it promotes a literary subjectivity firmly aligned with moral virtue (and very often at odds with the commercial public sphere). Austen’s courtship narratives are widely regarded as a high point of the ‘serious’ modern realist novel, understood precisely as a secular literary mode. To acknowledge Burney and Austen’s departures from their Anglican and Patriot predecessors is not to forget the legacy that shapes their work; it is, instead, to notice that in their hands the English marriage plot undergoes a profound and enduring transformation.
In the summer of 1753, while controversy over the Marriage Act and the Jewish Naturalisation Act was in full flow, Richardson, by then a successful London printer and a famous author, wrote to Elizabeth Carter in support of both bills. The letter has been understood to indicate that he was a proponent of the Court Whig programme. But that is not quite so. On the marriage question in particular, Richardson’s opinions differed from those which motivated Hardwicke’s legislation, even though his novels also rejected the modes of clandestine marriage that the legislation abolished.
This chapter explores the precise nature of Richardson’s affinities and differences with the Hardwicke legislation in the context of his two marriage-focussed novels, Pamela and The History of Sir Charles Grandison.
Why did marriage become central to the English novel in the eighteenth century? As clandestine weddings and the unruly culture that surrounded them began to threaten power and property, questions about where and how to marry became urgent matters of public debate. In 1753, in an unprecedented and controversial use of state power, Lord Chancellor Hardwicke mandated Anglican church weddings as marriage's only legal form. Resistance to his Marriage Act would fuel a new kind of realist marriage plot in England and help to produce political radicalism as we know it. Focussing on how major authors from Samuel Richardson to Jane Austen made church weddings a lynchpin of their fiction, The Origins of the English Marriage Plot offers a truly innovative account of the rise of the novel by telling the story of the English marriage plot's engagement with the most compelling political and social questions of its time.
The parade of sexualized personae that features in this chapter's title carries a history. Libertines, rakes, and dandies are figures that occur in a sequence that begins in the sixteenth century and effectively comes to an end by the twentieth century, although it is a sequence marked by overlaps and ambiguities. Drawing on a rich body of scholarship, the chapter traces passages from the libertine through the rake and dandy, concentrating on each in turn. It focuses on metropolitan England, where, arguably, the libertine, the rake, and the dandy came most vividly to life. Libertinage has a long and complex history that reaches back into antiquity. In the fifteenth and sixteenth centuries, the category was mainly applied to a kind of writing that already held a firm place in manuscript culture. Rake is more concretely bound to particular sites and institutions than the libertine, and especially to a particular moment in the court's recent past.