Differential Effects of Psychotic Illness and Antipsychotics on the Brain
Sep 17
In this episode of The Biological Psychiatry Podcast, Dr. Elvisha Dhamala sits down with Dr. Sidhant Chopra from Orygen and the University of Melbourne to discuss his recent paper published in Biological Psychiatry.
When we see changes in the brain in someone with psychosis, is that the disease itself, or a side effect of the medications we're prescribing to treat it? This question has been surprisingly difficult to answer, because almost everyone who develops psychosis is immediately started on antipsychotic medication, making it nearly impossible to distinguish what the illness does to the brain from what the drugs do. In this conversation, we explore how Dr. Chopra and his colleagues at Orygen, the University of Melbourne, and Monash University, addressed this question using a triple-blind, randomized, placebo-controlled trial in people experiencing their very first episode of psychosis who had never taken antipsychotic medication. Dr. Chopra walks us through the remarkable finding that patients on placebo showed widespread cortical thinning over 12 months while patients on antipsychotics did not, why the regional pattern of thinning may reflect the underlying neurobiology of psychosis, and how the spatial pattern of thinning aligned with normative distributions of specific neurotransmitter receptors. We also discuss the challenges of running a placebo-controlled trial in psychosis, why a null result in the antipsychotic group isn't the same as evidence of neuroprotection, and what the transdiagnostic nature of the sample means for generalizability. The conversation closes with a look at what these findings mean for how we think about the earliest brain changes in psychosis and the role of antipsychotic medication.
Paper:
DOI: 10.1016/j.biopsych.2026.06.028
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