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Trauma is prevalent amongst early psychosis patients and associated with adverse outcomes. Past trials of trauma-focused therapy have focused on chronic patients with psychosis/schizophrenia and comorbid Post-Traumatic Stress Disorder (PTSD). We aimed to determine the feasibility of a large-scale randomized controlled trial (RCT) of an Eye Movement Desensitization and Reprocessing for psychosis (EMDRp) intervention for early psychosis service users.
A single-blind RCT comparing 16 sessions of EMDRp + TAU v. TAU only was conducted. Participants completed baseline, 6-month and 12-month post-randomization assessments. EMDRp and trial assessments were delivered both in-person and remotely due to COVID-19 restrictions. Feasibility outcomes were recruitment and retention, therapy attendance/engagement, adherence to EMDRp treatment protocol, and the ‘promise of efficacy’ of EMDRp on relevant clinical outcomes.
Sixty participants (100% of the recruitment target) received TAU or EMDR + TAU. 83% completed at least one follow-up assessment, with 74% at 6-month and 70% at 12-month. 74% of EMDRp + TAU participants received at least eight therapy sessions and 97% rated therapy sessions demonstrated good treatment fidelity. At 6-month, there were signals of promise of efficacy of EMDRp + TAU v. TAU for total psychotic symptoms (PANSS), subjective recovery from psychosis, PTSD symptoms, depression, anxiety, and general health status. Signals of efficacy at 12-month were less pronounced but remained robust for PTSD symptoms and general health status.
The trial feasibility criteria were fully met, and EMDRp was associated with promising signals of efficacy on a range of valuable clinical outcomes. A larger-scale, multi-center trial of EMDRp is feasible and warranted.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by gradual memory loss and declining cognitive and executive functions. AD is the most common cause of dementia, affecting more than 50 million people worldwide, and is a major health concern in society. Despite decades of research, the cause of AD is not well understood and there is no effective curative treatment so far. Therefore, there is an urgent need to increase understanding of AD pathophysiology in the hope of developing a much-needed cure. Dissecting the cellular and molecular mechanisms of AD pathogenesis has been challenging as the most commonly used model systems such as transgenic animals and two-dimensional neuronal culture do not fully recapitulate the pathological hallmarks of AD. The recent advent of three-dimensional human brain organoids confers unique opportunities to study AD in a humanised model system by encapsulating many aspects of AD pathology. In the present review, we summarise the studies of AD using human brain organoids that recapitulate the major pathological components of AD including amyloid-β and tau aggregation, neuroinflammation, mitochondrial dysfunction, oxidative stress and synaptic and circuitry dysregulation. Additionally, the current challenges and future directions of the brain organoids modelling system are discussed.
Previous research in resting-state functional magnetic resonance imaging (rs-fMRI) has shown a mixed pattern of disrupted thalamocortical connectivity in psychosis. The clinical meaning of these findings and their stability over time remains unclear. We aimed to study thalamocortical connectivity longitudinally over a 1-year period in participants with recent-onset psychosis.
To this purpose, 129 individuals with recent-onset psychosis and 87 controls were clinically evaluated and scanned using rs-fMRI. Among them, 43 patients and 40 controls were re-scanned and re-evaluated 12 months later. Functional connectivity between the thalamus and the rest of the brain was calculated using a seed to voxel approach, and then compared between groups and correlated with clinical features cross-sectionally and longitudinally.
At baseline, participants with recent-onset psychosis showed increased connectivity (compared to controls) between the thalamus and somatosensory and temporal regions (k = 653, T = 5.712), as well as decreased connectivity between the thalamus and left cerebellum and right prefrontal cortex (PFC; k = 201, T = −4.700). Longitudinal analyses revealed increased connectivity over time in recent-onset psychosis (relative to controls) in the right middle frontal gyrus.
Our results support the concept of abnormal thalamic connectivity as a core feature in psychosis. In agreement with a non-degenerative model of illness in which functional changes occur early in development and do not deteriorate over time, no evidence of progressive deterioration of connectivity during early psychosis was observed. Indeed, regionally increased connectivity between thalamus and PFC was observed.
In Frisch's narrative Montauk (1975), various memories and episodes from the narrator's life are alternately presented from a first-person and a third-person point of view. throughout the text, the writing process of this specific book, and of literature in general, are negotiated in a self-referential discourse. The time frames change frequently. Fragmentary and constantly shifting memories that reach back into childhood are interwoven with a present-day plot set in the United States. This plot shows the sixty-two-year-old narrator “Max” in 1974 with Lynn, a young American woman whom he met at his New York publisher's office and with whom he spends a few days in New York City and a weekend at the shore, in Montauk, on the far eastern end of Long island.
The work's narrative structure is highly complex. The pages written in the past tense are partially grouped according to thematic clusters and partially follow a loose associative pattern. The thematic segments present aspects of the life of “Max,” a Swiss writer, in brief episodes or diachronically under thematic titles such as “architecture” or “fame,” and shed light on his experiences and character traits. Another technique of weaving the diverse segments together uses subtle associations that are triggered by persons, places, objects, time references, questions, single words, and quotations, associations that establish parallels between the present and a remembered past. Particularly memories of other people are interwoven in an associative manner. They provide connections to the narrated time in Montauk.
Frisch's novel stiller (1954) begins with an exclamation: “Ich bin nicht Stiller!” (I'm not Stiller!) The novel's protagonist, Anatol Stiller, a Swiss sculptor who has taken on a new identity and moved to the United States and then to Mexico, returns to his home country and is arrested upon his arrival after an altercation with a Swiss border guard who questions the validity of his identification papers. The novel consists of two parts, a journal that Stiller writes in a series of notebooks while in pre-trial confinement, and an account in which the district attorney, who had become a friend of Stiller's, outlines Stiller's life after his release. Throughout Stiller's notebooks, the prisoner claims that his name is not Stiller, but James White, a position that he continues to insist on even when his wife confronts him. Like many of Frisch's works, the novel negotiates conflicts between subjective and external reality and questions the stability of selfhood. The notebooks display a clear structure. Segments on Stiller's wife Julika and on the district attorney Rolf and his wife Sibylle alternate with reflections, dialogues, and stories that Stiller/White invents for his prison guard in order to entertain him while at the same time revealing a lot of himself.
Max Frisch's tagebücher mainly consist of Tagebuch 1946–1949 (1950) and Tagebuch 1966–1971 (1972). The first volume received close attention only after the second was published and rapidly became a bestseller in 1972, with extremely positive reviews by Rudolf Hartung and Marcel Reich-Ranicki in Die Zeit and by Hans Mayer in Der Spiegel. Thus, it is not surprising that the first volume to be translated into English, in 1974, was the Tagebuch 1966–1971 (under the English title Sketchbook 1966–1971), followed a few years later, in 1977, by the Tagebuch 1946–1949 (Sketchbook 1946–1949), more than twenty-five years after its first publication in German.
Yet Tagebuch 1946–1949 was not the first Tagebuch written by Max Frisch. Indeed, besides the Tagebuch with Marion—the first part of the Tagebuch 1946–1949, covering the years 1946 and 1947, which had already been published in 1947—Frisch had written Blätter aus dem Brotsack (Pages from the Knapsack) in 1939, which was his first longer prose work after the novels Jürg Reinhart (1934) and Antwort aus der Stille (An Answer from the Silence, 1937). Blätter aus dem Brotsack was also the first work that Max Frisch wrote after he had burned his unpublished manuscripts in 1937 and had decided never to write again (Tb 1, 588). As Frisch explained later in an interview with Rolf Kieser, in this very particular situation he naturally chose the diary form because he did not have enough time for longer literary forms.
Max Frisch was sixteen when he sent his first play, Stahl (Steel), to Max Reinhardt at the Deutsches Theater in Berlin, but when the rejection slip came back from Berlin, the play was consigned to flames. So it was not in 1937, but as early as 1927 that he first voluntarily destroyed some of his own writings. The play had been typed on a rented typewriter, for which Frisch had to use his pocket money. That is perhaps why he was writing in a hurry. However, the rejection from Berlin did not give rise to any sense of resignation or self-doubt; on the contrary, Frisch immediately began writing a new play.
We do not know what exactly he destroyed in 1937 when he went into a forest to consign all his unpublished early manuscripts to the flames. Frisch said that his diaries were among the irretrievably lost texts. They probably also included the play Der Schüler im Himmel (Schoolboy in Heaven), which he wrote in March 1927 for a school performance, and also presumably the three-act play entitled 13. Trupp (Troop 13), which was announced for a family evening of the Free Military Preparatory Training organization (F.M.V.) in 1928. Was the manuscript of Flucht (Escape), which he had sent to his friend Werner Coninx to look at in 1935, among the works destroyed?
Wir [sind] denn doch keine kybernetischen Mäuse, gesteuert von “information” und “feed back” und basta.
[After all, we are not cybernetic mice, guided by “information” and “feedback,” once and for all.]
—Max Frisch, Biografie: Ein Spiel
The American author Kurt Vonnegut proclaimed, “novels that leave out technology misrepresent life as badly as Victorians misrepresented life by leaving out sex.” If Vonnegut was correct, then Max Frisch's 1957 novel Homo Faber is a remarkably accurate representation of life. Although there is a tendency in some of the secondary literature, as noted by Ferdinand van Ingen in his article on technology and mythology in Homo Faber, to view the protagonist Walter Faber's occupation and his obsession with all things technological as more or less coincidental, and although Frisch himself gave conflicting answers regarding Faber as a “Techniker,” I suggest that technology is indeed a key to understanding this novel. Faber's former lover Hanna Landsberg puts it best when she describes technology as a trick that allows humans to order the world in such a way “daßwir sie nicht erleben müssen” (so that we don't have to experience it). This is Faber's goal. Throughout the text he denigrates “Erlebnisse” and the idea of “erleben.” His connection to the natural world is filtered or mediated by technology, and Faber claims to prefer it that way.
Literary scholars and critics have not discussed Max Frisch's essays and speeches in a comprehensive manner yet, even though they constitute a considerable part of his prose texts and develop thematic threads found throughout the fabric of his work. the recipient of numerous literary prizes, Frisch used the genre of award acceptance speeches to reflect on creative tensions between aesthetic curiosity and ethical responsibility. His essays and speeches can be read as one continuous text throughout which Frisch juxtaposes the conflicting but mutually enriching voices of the writer as an artist whose projects are playfully open-ended and a concerned global citizen who discusses world affairs. While Frisch's essays inhabit a border zone between artistic exploration and political engagement, he disliked the notion of littérature engagée.
It is impossible to discuss the full range of Frisch's essayistic work and his speeches in this chapter. the following discussions focus on Frisch's central thematic clusters: the ethics and poetics of writing and theater, global and Swiss politics, and existential questions of death and hope.
On Literature and Political Activism
Beginning in the 1930s, Frisch's essays explore the relationship of epistemic desire and the art of the narrative, as well as an anthropological condition that he calls, in the title of an essay published in 1960, “Unsere Gier nach Geschichten” (Our Greed for Stories). For Frisch, literature embodies at once a continuous, open-ended aesthetic experiment and a medium for undogmatic political engagement.
Why should we read Max Frisch (1911–91) in the twenty-first century? Because his works relentlessly examine an acutely crippling human condition, our addiction to turning ourselves and others into passive recipients of fixed images and projections. But beyond the undiminished relevance of this main thematic thread that runs through all of Frisch's works, his sparse and precise prose style generates a rare level of aesthetic and intellectual pleasure that reintroduces his readers to the intense joy of thinking through what it could mean to be human. The introspective playfulness of this classic writer of late modernism seduces readers to immerse themselves in Socratic skepticism. Frisch's sketch-books, fictional prose, plays, essays, and speeches offer the reader useful and stimulating antidotes against complacent catchwords and prescriptive solutions that mask the personal crises and social conflicts of today's over-medicated societies. Frisch challenges us to think through who we are by inviting us to imagine who else we might have been.
Nobody has outlined the resilience of curiosity that is at the core of our assessment of Frisch more lucidly than Stefan Zweig. In a letter to his fellow exiled writer Hermann Kesten composed in Petropolis, Brazil, on January 15, 1942, Zweig explains his interest in the French philosopher Montaigne in a way that may also serve as an elucidation of Frisch's continuing relevance to readers in the twenty-first century.
In an interview published in Die Zeit in 2010, Swiss actor Bruno Ganz, one of the most influential artists in the German-speaking world over the last fifty years, insists on the unreliability and fluid status of personal identity:
Ich halte es nicht für einen allzu gesicherten, fest umrissenen Zustand, der zu sein, der ich bin. Ich denke, Identität besteht aus allen möglichen ungeklärten teilen. Und was ist eigentlich dieses “Ich”? Ich versuche, das fliessend zu halten, weil ich Angst vor festen Grenzen habe. andererseits merke ich schon, dass es so etwas wie “mich” gibt. Oder Dinge, die sich einfach immer wieder ereignen, wenn ich dabei bin.
[I do not consider being who I am a well secured and rigidly defined condition. I believe that identity consists of all kinds of possible unexplained components. And what is this “I” in the first place? I try to keep it fluid because I am afraid of static boundaries. On the other hand I notice that there is something like “me.” Or things that happen time and again when I happen to be around.]
Arguing against a static conception of autobiographical coherence, Ganz, whose early theater career at the Zurich Schauspielhaus had been supported by Frisch when he urged the city of Zurich not to close the Schauspielhaus, puts the fragility of selfhood and a productive fear of fixed boundaries at the heart of self-understanding.
The theme ofAndorra: Ein Stück in zwölf Bildern (Andorra: A Play in Twelve Scenes, 1961), both as a geographical topos and as an allegory of isolation and narrowness, absorbed Max Frisch since the early stages of his career. In Frisch's Tagebuch 1946–1949, one finds a first reference to the small state: “Andorra ist ein kleines Land, sogar ein sehr kleines Land, und schon darum ist das Volk, das darin lebt, ein sonder-bares Volk, ebenso mißtrauisch wie ehrgeizig, mißtrauisch gegen alles, was aus den eigenen Tälern kommt” (Andorra is a small country, very small indeed, and just for this very reason the people living there are odd people, as distrustful as they are ambitious, suspicious of everything even when it comes out of their own valleys). A few entries later, under the heading “The Andorran Jew,” Frisch converges the thematic complex in one person who will eventually evolve into the main character of the play, a young man who was believed to be a Jew and onto whom everyone projected a ready-made image, “das fertige Bildnis, das ihn überall erwartet” (372; the fixed image that meets him everywhere: 19).