Philip K. Dick (1928–1982) was one of the most influential and prolific American science fiction writers of the twenty-first century, with many of his books having been adapted into popular movies, including Total Recall, Blade Runner, Minority Report and A Scanner Darkly. His writing is revered for its engrossing accounts of characters who exist on the fringe, alienated and operating in the shadows of authoritarian alternative universes. His protagonists, often plagued by substance abuse and escalating paranoia, spiral into states of disassociation or delusions — the crisis of their mounting unease unfolding into a break from so-called reality. Arguably, what makes these counterculture heroes so authentically appealing was that Dick’s own life was marked by chronic methamphetamine addiction, periods of profound psychological disturbance, visual hallucinations and, according to Dick himself, episodes of psychosis.

The alternative text for this image may have been generated using AI.
Credit: stellalevi / DigitalVision Vectors / Getty

The portmanteau ‘psychosis’ (psychic neurosis) applied to psychiatric disorders has been in use since the 1840s. But in modern terms, psychosis refers broadly to a complex assemblage of symptoms that spans cognitive dimensions, such as confusion, disorganized patterns of thinking and delusions, to sensory features, including hallucinations that are visual, gustatory and auditory in nature. People who are experiencing psychosis may also exhibit changes in appetite, sleep or social activity as well as a pervasive sense that something is wrong. As Dick succinctly described, “Let it be said that one of the first symptoms of psychosis is that the person feels perhaps he is becoming psychotic”.

Descriptions of psychosis offer an intriguing entrance into the complex nosological conundrums that surround it. At its most elemental level, psychosis is considered a cluster of symptoms but is also often referred to as a qualifying symptom of specific disorders. Although no longer a strictly categorical system, the current iteration of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) assesses features of psychosis in relation to other symptoms. This establishes the presence of hallucinations, for example, to determine whether criteria is met for a primary psychotic disorder, such as schizophrenia or bipolar disorder, or to diagnose “secondary psychosis” associated with a general medical condition or that may be induced by substance intoxication or withdrawal.

By contrast, newer dimensional approaches applied to psychosis, such as the National Institute of Mental Health’s Research Domain Criteria (RDoC) or the Hierarchical Taxonomy of Psychopathology (HiTOP) frameworks have gained momentum by shifting the focus to common measurable dimensions or symptom components of psychosis. A core appreciable utility of approaches that are dimensional becomes apparent when establishing more general risk profiles for developing an episode of psychosis. Although psychosis can occur across the lifespan, it more frequently emerges during late adolescence and early adulthood, underscoring the need to identify the first episode of psychosis (FEP) or early psychosis as a crucial window for intervention, as opposed to diagnosis with a psychotic disorder more specifically.

The April 2025 issue of Nature Mental Health features two papers investigating the FEP period, but from different vantage points. Mana et al. explore whether neurobiological markers can be used to characterize functioning in people with early psychosis who have remitted or who have not. Using functional magnetic resonance imaging (fMRI) and diffusion spectrum MRI, the authors assessed resting state functional connectivity in groups that differ in clinical status staging (that is, first episode, remission with relapse and non-remitting) who were compared with healthy control participants. The authors identify distinct differences in functional strength across brain regions associated with remission from psychosis that may reflect compensatory processes and help to refine models of neural and clinical functioning across stages of psychosis.

For many people who have contact with psychiatric care for a FEP, antipsychotics typically become the first line of treatment. Poor adherence to oral antipsychotics, subsequent relapse and hospitalization are common, however, making long-term studies of subgroups of people with early psychosis challenging to conduct. Long-acting injectable (LAI) antipsychotic treatment may be a useful alternative but the findings of previous studies have been mixed. Szmulewicz et al. offer a new way to examine the effects of LAI therapy by using an emulation trial design to leverage data from the largest existing clinical trial and additional observational cohorts. Using the emulation trial technique, the authors present findings that the initiation of LAI therapy reduces psychotic relapse over three years. In the absence of larger and long-term trial data, emulation trial data provide support for further consideration of long-acting antipsychotic treatments as the standard of care for many people with early psychosis.

We also announce the launch of a new Collection on psychosis. The Psychosis collection features primary research providing insights and investigations across the range of disorders that are characterized by psychosis and will actively encourage the discussion of categorical and dimensional approaches in the service of refining future research directions. The Collection will also feature commentary and views from, and that focus on, people with lived experience of psychosis.

Much like each generation of readers who are drawn anew to Dick’s stories of futuristic disenfranchisement, psychosis is an enduringly fascinating and challenging topic for mental health scholars and practitioners. Perhaps so because in our attempts to understand the mechanisms that can produce such profound disconnection, it is an opportunity to engage with themes that relate to our essential interrelatedness, our humanity and to exercise empathy. Dick certainly agreed: “Mankind needs more empathy”.