“…Yet, first-line pharmacotherapies still rely on putative molecular mechanisms of action that derive from serendipitous observations dating back to the 1950s (Braslow and Marder, 2019), and, despite some progress in development of novel therapies (Brannan et al, 2021;Brunoni et al, 2017;Carhart-Harris et al, 2021;Daly et al, 2019;Davis et al, 2021;Koblan et al, 2020;McClure-Begley and Roth, 2022;Mitchell et al, 2021;Popova et al, 2019), both pharmacological and psychological interventions remain ineffective for many patients (Malhi and Mann, 2018;McCutcheon et al, 2020;Simmonds-Buckley et al, 2021). It might be argued that this attests to the unique complexity of psychiatric disorders, where causal pathways are assumed to reflect an interplay of psychological, environmental, socio-cultural, genetic, and other biological factors (Singh et al, 2022;Sterling and Platt, 2022;Trubetskoy et al, 2022;Taylor et al, 2022). Despite this causal complexity, a core tenet of clinical cognitive neuroscience is that psychiatric symptoms are an expression of potentially identifiable altered neurophysiological function (a proximate cause), reflecting a multiplicity of upstream biopsychosocial causal factors (Deisseroth, 2021).…”