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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 neurobiology of trichotillomania (TTM) has only recently received attention from the neuropsychiatrie community, and the number of studies in this area is limited. Nevertheless, there is tentative support for the hypothesis that serotonergic, dopaminergic, and opioid systems mediate hair-pulling symptoms, and that corticostriatal circuits also play a role. An understanding of the neurobiology of TTM may be of value not only for the treatment of this disorder, but also for other stereotypic behaviors.
Two early examples suggest the importance of visual art in Dickens’s conception of his own role. One is the title of his first book, Sketches by Boz and Cuts by Cruikshank, which doubly insists (the parallel of the two artists, the author as sketcher) upon the similarities of writing and drawing. The other is the first image in the last number of Nicholas Nickleby, Daniel Maclise’s portrait of Dickens, subsequently incorporated as the frontispiece to the first edition (figure 1), a formal representation of the writer and the fact of his literary success. Replacing the fourth illustration of the final number, in some sense this image also illustrates; but rather than picturing some portion of the text, the portrait refers beyond it and beyond the writer’s mere textual presence to his life as a public figure. We see Charles Dickens supplanting Boz, a personage emerging from a pseudonym, his face rather than his prose the guarantor of identity, as if visuality has replaced the uncertainty of a mere name, mere words, with a self both recognizable and authentic (“Faithfully yours,” as the valediction over his signature declares). With this new public image attached to his writing, Dickens complicates the very conception of his “identity” (a term that can refer to the singular essence of some thing or person as well as to its equivalence to something or someone else): to know the writer we must see his face – see it, that is, formally rendered by a major contemporary painter. Presenting the “real” Dickens with a picture, illustrating the author, the portrait locates both the writer and his fiction within Victorian visual culture.
Gold labels such as Nanogold® and colloidal gold are enlarged and visualized in the electron microscope or optically by the selective deposition of silver onto their surfaces. This process, known as autometallography (AMG), silver amplification or silver enhancement, is initiated by exposing the particles to a solution containing silver (I) ions and a reducing agent such as hydroquinone or npropyl gallate. Particles may be enlarged to between 30 and 100 nm in diameter, giving a distinctive black, punctate staining in the light microscope. Nanogold® labeling with silver amplification is one of the most sensitive methods available for histopathology applications such as in situ hybridization. With Catalyzed Reporter Deposition (CARD; also called Tyramide Signal Amplification, or TSA® ; NEN Life Sciences, Boston MA), it has been used to detect as few as 1-2 copies of viral DNA or RNA per cell. However, its uses are restricted by reactions of silver (I) with halides and other elements in tissues. Also, after signal development, self-nucleation and non-specific background deposition begin quickly, which can make end-point selection difficult or prevent incorporation into automated procedures.
The Poetry of Architecture, Ruskin's first collection of essays, is even more “deformed by assumption” than his autobiography admits. Architecture is defined as poetic for genteel tourists, who forget that the buildings whose beauty they admire required human labor and embody distinctions of class. Indeed, architectural poetry expresses a myth of class harmony: buildings blending into the landscape, landowners welcomed by loving tenants. Yet this vision, though apparently sanctified by nature, is threatened—by industrial landscapes, cities, and less appealing aspects of nature itself. Without poetry, architecture might seem little more than the sort of instinctive shelter building we observe in the lower animals, hence suggestive of biological kinship between human beings and “brutes.” At the heart of Ruskin's architectural dreams is a feared disappearance of all distinctions, biological as well as social—a pre-Darwinian nightmare.
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