Major Changes in the Treatment of Schizophrenia: A Long Time in the Making

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SPECIAL REPORT: SCHIZOPHRENIA & PSYCHOSIS

In this Special Report, you will find 3 articles on the state of schizophrenia research and treatment, including a report of a Texas-based first-episode specialty treatment service, an update on how the neuroscience of schizophrenia is moving from a dysfunctional neurotransmitter model to disruptions in neuronal circuitry, and an article showing that early childhood adversity and trauma are now established as causal risk factors for psychosis and schizophrenia during later adolescence.

Coordinated Specialty Care

The needs of young and vulnerable individuals with recent-onset psychosis differ from those who have more chronic illnesses. In the first article, the specialty team uses a recovery model of schizophrenia, working on the assumption that early intervention can alter the course of schizophrenia toward better outcomes than had previously been considered possible. Therefore, interventions are oriented toward returning to competitive employment or resuming academic pursuits, using pharmacologic and psychosocial treatments that align with these goals.

The origin story for first-episode specialty programs comes from Australia. Back in the late 1980s, the city of Melbourne started a specialty care program that just admitted young adults experiencing recent-onset psychosis.¹ The idea was to avoid the stigma of public mental health services and tailor the program to the needs of individuals and their families while in the early stages of psychosis. This unit became a regional outpatient specialty service and was then adapted by the national Australian mental health system. Its success became a model for similar programs in other countries, including the UK, Netherlands, and Canada. Until recently, the US lagged behind.

Despite the appeal, there are concerns. First-episode programs are not universally available in the US. Additionally, these programs are expensive and ideally need additional resources apart from existing mental health budgets. Otherwise, funding may divert resources and staff from within the local mental health system. Finally, there is a concern about whether the benefits of these programs will endure beyond 2 to 5 years of participation.² We need to address these concerns to properly use first-episode programs in the US.

Early Adversity

Childhood trauma and adversity are risk factors for schizophrenia. Most readers based in the US probably think of schizophrenia as a purely biological, genetic, or medical condition. In the 1970s, research in schizophrenia soundly rejected social causation theories and embraced biological theories. Those familiar with the notorious “schizophrenogenic mother” understand the dangers of an inaccurate social causation model. Childhood traumas, such as neglect, bullying, and physical or sexual abuse, were risk factors for many psychiatric diagnoses, but the risk of schizophrenia was somehow spared.

It is not that simple. Traumatic experiences in childhood increase the future risk of psychosis and having a schizophrenia diagnosis. Advances in epidemiologic techniques with the availability of long-term cohort studies have shown a clear relationship between childhood trauma and the future risk of a psychotic disorder, including schizophrenia.³ While the risk factor of childhood adversity is no longer in debate, it does not contradict the biological or genetic origins of schizophrenia.⁴ Schizophrenia, like many other complex diseases, has gene-environment interactions. In other words, individuals with genetic or biological predispositions may be more vulnerable to the consequences of childhood adversity than others who are less predisposed.

Circuits, Not Synapses

On a fundamental level, what is emphasized in neuroscience also determines to some extent how to differentiate normal vs dysfunctional brain functioning and its behavioral consequences. In the third article, the author shows us changes in understanding how dopaminergic systems relate to schizophrenia symptoms. Reading this is like watching a time-lapse photograph showing how a tree changes over 4 seasons, but instead of a year, it is shown over a minute. We see how the early versions of the dopamine hypothesis relied heavily on “too much” dopamine at specific neuronal sites and how these synaptic sites’ dopamine receptors were blocked by medications that reduced symptoms of schizophrenia. Compare that with the 75-year fast forward of dopaminergic circuitry and complex branched signaling, and the subtleties of these shorter and longer circuits show in relationship to the ligand in question (in this case, dopamine) and other neurotransmitter pathways.⁵

Concluding Thoughts

These 3 articles each reflect major changes in the treatment of schizophrenia. One shared feature is that the changes and progress covered have all been a long time in the making. They also show how much our advances have resulted from a worldwide network of clinicians, epidemiologists, and neuroscientists. How has this changed since the 1980s? The first-episode programs show our changing understanding that long-term trajectories are at least partly dependent on what we offer early on, that prevention of schizophrenia might focus on preventing or mitigating harmful effects of childhood trauma, and that neuroscientific models that are amenable to new approaches may lead to better or safer pharmacologic treatments in the future.

On a personal note, I am thrilled to be the Schizophrenia Special Report chair. I want to thank our Editor-in-Chief, John J. Miller, MD, and the Psychiatric Times editorial team —Heidi and Leah, for their work on this issue.

Dr Weiden is a clinical professor of psychiatry at the Renaissance School of Medicine at Stony Brook University in New York. He is the Schizophrenia and Psychosis Section Editor for Psychiatric Times.

References

1. McGorry PD, Edwards J, Mihalopoulos C, et al. EPPIC: an evolving system of early detection and optimal management. Schizophr Bull. 1996;22(2):305-326.

2. Hansen HG, Starzer M, Nilsson SF, et al. Clinical recovery and long-term association of specialized early intervention services vs treatment as usual among individuals with first-episode schizophrenia spectrum disorder: 20-year follow-up of the OPUS trial. JAMA Psychiatry. 2023;80(4):371-379.

3. Croft J, Heron J, Teufel C, et al. Association of trauma type, age of exposure, and frequency in childhood and adolescence with psychotic experiences in early adulthood. JAMA Psychiatry. 2019;76(1):79-86.

4. Arseneault L, Cannon M, Fisher HL, et al. Childhood trauma and children’s emerging psychotic symptoms: a genetically sensitive longitudinal cohort study. Am J Psychiatry. 2011;168(1):65-72.

5. Howes OD, Dawkins E, Lobo MC, et al. New drug treatments for schizophrenia: a review of approaches to target circuit dysfunction. Biol Psychiatry. 2024;96(8):638-650.