Intergenerational neuroimaging’s present and future: Considering sex as a biological variable to enhance knowledge of brain development through parent–offspring similarity

Intergenerational neuroimaging, which is used to investigate brain similarities between parent-offspring dyads, promises to elucidate the neural substrates of intergenerational transmission. However, merely identifying similar brain regions or networks between parents and offspring is not sufficient to reveal the mechanisms underlying this transmission. To understand these mechanisms, it is necessary to consider the potential contributions of shared genetic and environmental factors to the development of brain features that are similar between parents and offspring. Sex as a biological variable (SABV), a key factor in intergenerational neuroimaging, provides crucial insights into brain development. Although sex-based differences in brain developmental trajectories have been investigated, the role of SABV in parent-offspring brain similarity has been overlooked. In this narrative review, we summarize the key findings of previous intergenerational neuroimaging studies, grouping them into three categories based on study design: studies of mother-offspring dyads, studies combining fathers and mothers, and studies distinguishing between father-offspring and mother-offspring dyads. Furthermore, we highlight the genetic and environmental factors that may underlie sex-specific parent-offspring brain similarities. Finally, we propose further considerations to clarify the significance of parent-offspring brain similarity in human brain development. Advancements in intergenerational neuroimaging may shed light on mechanisms by which mental health risk is transmitted across generations, potentially providing opportunities for more effective prevention, stratification, and treatment.