Joseph Guislain's writings on melancholia from 1835 and 1852.

Over the course of the 19th century, the concept of melancholia morphed from a partial insanity defined by disorders of judgment to a disorder characterized primarily by mood disturbances. The francophone Belgian psychiatrist Joseph Guislain, whose work has not been previously translated into English, played an important role in this transition. We translate and comment upon two of his key descriptions of melancholia from 1835 and 1852, emphasizing the following 5 features. First, his concept of melancholia is quite "modern" meeting all DSM-5 criteria for major depression. Second, his clinical descriptions are vivid, often giving voice to his patients. Third, other aspects of his text reflect older concepts, including 17th century melancholic subtypes. Fourth, and of particular historical import, he was, in 1835, likely the first major European alienist to argue that nonpsychotic melancholia was an important form of the disorder and a legitimate mental illness. This represented key step in the transition of melancholia from a psychotic to a mood disorder and also helped expand the 18th century model of insanity which was as restricted solely to disturbances of judgment/imagination. Fifth, beginning with his 1835 writings, but more prominently in his 1852 text, Guislain emphasizes that melancholia is a form of phrenalgia - mental pain. In so doing, he played an important role in helping initiate this influential psychophysiological theory of melancholia that was championed by Wilhelm Griesinger and other important German and English psychiatrists later in the 19th century.

William Boven's 1915 thesis "Similarity and Mendelism in the heredity of dementia praecox and manic-depressive insanity".

Boven published, in 1915, his MD thesis at the University of Lausanne in which he examined 60 3- to 4-generation pedigrees ascertained from admitted patients with dementia praecox (DP) and manic-depressive insanity (MDI). He asked three questions: (i) were DP and MDI hereditary? (ii) were they the same or distinct conditions? and (iii) were they Mendelian disorders? Based on the rarity of environmental precipitants severe enough to cause disorder onset and the pattern of disorders in relatives, Boven concluded that both disorders were inherited. He found that MDI largely ran in families through direct transmission across generations while DP was only common in collateral relatives. Both pedigrees contained a substantial number of "psychopathic" (personality disordered) relatives in which DP and MDI pedigrees typically had, respectively, paranoid, and dysthymic/cyclothymic features. Boven concludes that their inheritance is largely distinct but not exclusive, as some pedigrees contained cases of both disorders. With assistance from Wilhelm Weinberg, Boven applied algebraic models with proband correction to rates of DP and MDI in sibships and found the results inconsistent with Mendelian transmission. His study represents among the first examinations, using "modern" methods, of the familial relationship between DP and MDI and the first published in French.

The Development of Non-affective Psychotic Syndromes in the 19th Century: LeGrand du Saulle and His 1871 Monograph "Le Délire De Persécutions" (Persecutory Delusions).

While the origins of two of Kraepelin's three subtypes of dementia praecox (DP), catatonic and hebephrenic, are well understood, no similar clear narrative exists for his concepts of paranoia and paranoid DP, which require a consideration of both German and French sources. An important milestone in the French literature is the massive 524 page monograph entitled "Le Délire Des Persécutions" published in 1871 by Henri Legrand du Saulle which contained extensive, clinically detailed descriptions of a wide range of cases with prominent, organized persecutory delusions. Many of his cases reported auditory hallucinations (AH), and some bizarre, Schneiderian delusions. The delusional content could evolve to include prominent somatic and/or grandiose themes. Using a symptomatic diagnostic framework, Legrand du Saulle proposed that this syndrome represented an independent "species" of mental illness. He sought to give a voice to the affected individuals, including a chapter devoted entirely to their writings. He described several clinically fascinating features of such patients including how often they moved residence to unsuccessfully flee their persecutors and how delusional beliefs could be communicated to spouses and relatives. Unlike Kraepelin, he was little interested in their course of illness or rates of deterioration, except to note that recoveries occurred in 20% of cases. The clinical richness of this work substantially exceeded that in the contemporaneous German literature. Most of the cases described by du Saulle would fit easily into the two major non-affective delusional syndromes articulated 28 years later in Kraepelin's famous 6th edition of his textbook: paranoia and paranoid DP.

Notch signaling regulates neural stem cell quiescence entry and exit in Drosophila.

Stem cells enter and exit quiescence as part of normal developmental programs and to maintain tissue homeostasis in adulthood. Although it is clear that stem cell intrinsic and extrinsic cues, local and systemic, regulate quiescence, it remains unclear whether intrinsic and extrinsic cues coordinate to control quiescence and how cue coordination is achieved. Here, we report that Notch signaling coordinates neuroblast intrinsic temporal programs with extrinsic nutrient cues to regulate quiescence in Drosophila. When Notch activity is reduced, quiescence is delayed or altogether bypassed, with some neuroblasts dividing continuously during the embryonic-to-larval transition. During embryogenesis before quiescence, neuroblasts express Notch and the Notch ligand Delta. After division, Delta is partitioned to adjacent GMC daughters where it transactivates Notch in neuroblasts. Over time, in response to intrinsic temporal cues and increasing numbers of Delta-expressing daughters, neuroblast Notch activity increases, leading to cell cycle exit and consequently, attenuation of Notch pathway activity. Quiescent neuroblasts have low to no active Notch, which is required for exit from quiescence in response to nutrient cues. Thus, Notch signaling coordinates proliferation versus quiescence decisions.