A primary goal of clinical neuroscience is to identify associations between individual differences in psychopathology and the brain. However, despite a significant amount of resources invested in this endeavor, few reliable neural correlates of psychopathology have been identified. A common suspect for this lack of success is the significant heterogeneity in symptoms observed in psychiatric disorders. However, this is not the only potential source of heterogeneity, as substantial heterogeneity is also observed in brain structure and function. Thus, for clinical neuroscience to identify reliable neural correlates of psychopathology, it will be necessary to better understand heterogeneity in both psychopathology and the brain. In this commentary, we suggest four shared principles that can help disentangle heterogeneity in both of these domains: (a) the brain and behavior should both be treated as complex measures, (b) a priori assumptions should be viewed with caution unless they can be replicated robustly in individuals, (c) complex models of individual differences require appropriate data to estimate them, and (d) the field would benefit from an increased focus on extensively measuring individuals, such as through the use of personalized models of psychopathology and neuroimaging data. Together, these shared principles can aid in better characterizing-and separating relevant and irrelevant-heterogeneity in measures of psychopathology and neuroimaging. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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