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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.
On November 7, 1917 Max Weber offered his comments on “Science as a Vocation” before an assembly of students and faculty at the University of Munich, declaring that “disenchantment” was an “inescapable condition” and “the fate of our times.” But history tells us that nothing is truly inevitable. Although modern European intellectual history is replete with narratives of disenchantment and religious decline, the fact remains that religious speculation and formal discourses of theology survived well through the end of the twentieth century. For intellectuals who have shed the last remnants of personal faith, the endurance of theology in late modernity may seem perplexing, a symptom of what Nietzsche called Unzeitgemäßigkeit, or a decalibration in time. Already in 1882 Nietzsche’s madman declared that “God is dead. God remains dead. And we have killed him.” But even the madman recognized that he had come “too early.” What he called the “tremendous event” of God’s death was “still on its way”; it had “not yet reached the ears of men.” Critics who harken to the madman’s prophesy may likewise insist that European religious thought is a remnant of an earlier and more pious age.
In November, 1917, the German sociologist Max Weber delivered a now-famous lecture, “Science as a Vocation,” before an assembly of students and faculty at the University of Munich. “The fate of our times,” he declared, “is characterized by rationalization and intellectualization and, above all, by the ‘disenchantment of the world.’” Weber intended this remark as a global characterization of a modern society in which the natural sciences and bureaucratic rationality had conspired to undermine confidence in religious values and traditional sources of meaning. But we may also take his words as a more general verdict on the condition of modern European thought at the dawn of the twentieth century, when intellectuals from across the continent looked upon the wreckage of the First World War as a turning point in civilization, as a violent end to the nineteenth century and a grim foretaste of the world to come. Weber himself remained in a posture of ambivalence: He feared that the higher ideals of the Enlightenment were “irretrievably lost” and that only the imperative of “economic compulsion” would prevail.
It is something of a truism that each age must work through the legacy of its predecessors. In the case of the nineteenth century, this obvious statement gains poignancy when one considers the novel challenges and possibilities of the eighteenth century, which was, after all, the age of the Enlightenment. In its many guises and national variations, the Enlightenment asserted provocative and epoch-making claims about the role of reason, science, and criticism vis-à-vis the traditional authority of religion, state, and received knowledge. It drew new roadmaps for the conscious and reflexive reform of society and the betterment of people. At its core, it articulated a new emancipatory project – at once philosophical and political – chiefly oriented toward the ideal of individual autonomy. The cultural, social, and political configuration that shaped the Enlightenment came to something of an end in the closing decade of the eighteenth century, partly through processes of internal critique but also, spectacularly, through the political collapse of the Old Regime. In the changed circumstances of the early nineteenth century, the Enlightenment fragmented into a multitude of contests over the meaning of its legacy. What is the status of reason, and what is its proper relationship to other modes of knowledge? What of religion? What is the key discipline or cultural form that will, depending on one’s perspective and priority, advance, hinder, or deepen the impulses of enlightenment? What are the promises and perils of the project of emancipation, and how might it be continued, radicalized, or restrained? Are there limits to the pursuit of individual autonomy? What is the proper relation between the past and the future, tradition and innovation? None of these questions admitted definitive answers, but they fueled creative efforts, debate, and conflict across a great range of intellectual and cultural pursuits.
The Cambridge History of Modern European Thought is an authoritative and comprehensive exploration of the themes, thinkers and movements that shaped our intellectual world in the late-eighteenth and nineteenth century. Representing both individual figures and the contexts within which they developed their ideas, each essay is written in a clear accessible style by leading scholars in the field and offers both originality and interpretive insight. This second volume surveys twentieth-century European intellectual history, conceived as a crisis in modernity. Comprised of twenty-one chapters, it focuses on figures such as Freud, Heidegger, Adorno and Arendt, surveys major schools of thought including Phenomenology, Existentialism, and Conservatism, and discusses critical movements such as Postcolonialism, , Structuralism, and Post-structuralism. Renouncing a single 'master narrative' of European thought across the period, Peter E. Gordon and Warren Breckman establish a formidable new multi-faceted vision of European intellectual history for the global modern age.
The Cambridge History of Modern European Thought is an authoritative and comprehensive exploration of the themes, thinkers and movements that shaped our intellectual world in the late-eighteenth and nineteenth century. Representing both individual figures and the contexts within which they developed their ideas, each essay is written in a clear accessible style by leading scholars in the field and offers both originality and interpretive insight. This first volume surveys late eighteenth- and nineteenth-century European intellectual history, focusing on the profound impact of the Enlightenment on European intellectual life. Spanning twenty chapters, it covers figures such as Kant, Hegel, Wollstonecraft, and Darwin, major political and intellectual movements such as Romanticism, Socialism, Liberalism and Feminism, and schools of thought such as Historicism, Philology, and Decadence. Renouncing a single 'master narrative' of European thought across the period, Warren Breckman and Peter E. Gordon establish a formidable new multi-faceted vision of European intellectual history for the global modern age.