A call to leverage a health equity lens to accelerate human neuroscience research

Investigation of health inequities tend to be examined, in human neurosciences, as biological factors at the level of the individual. In actuality, health inequities arise, due largely in part, to deep-seated structural factors. Structural inequality refers to the systemic disadvantage of one social group compared to others with whom they coexist. The term encompasses policy, law, governance, and culture and relates to race, ethnicity, gender or gender identity, class, sexual orientation, and other domains. These structural inequalities include but are not limited to social segregation, the intergenerational effects of colonialism and the consequent distribution of power and privilege. Principles to address inequities influenced by structural factors are increasingly prevalent in a subfield of the neurosciences, i.e., cultural neurosciences. Cultural neuroscience articulates the bidirectional relationship between biology and environmental contextual factors surrounding research participants. However, the operationalization of these principles may not have the intended spillover effect on the majority of human neurosciences: this limitation is the overarching focus of the present piece. Here, we provide our perspective that these principles are missing and very much needed in all human neuroscience subdisciplines to accelerate our understanding of the human brain. Furthermore, we provide an outline of two key tenets of a health equity lens necessary for achieving research equity in human neurosciences: the social determinants of health (SDoH) framework and how to deal with confounders using counterfactual thinking. We argue that these tenets should be prioritized across future human neuroscience research more generally, and doing so is a pathway to further gain an understanding of contextual background intertwined with the human brain, thus improving the rigor and inclusivity of human neuroscience research

Contextualizing the impact of prenatal alcohol and tobacco exposure on neurodevelopment in a South African birth cohort: an analysis from the socioecological perspective

BackgroundAlcohol and tobacco are known teratogens. Historically, more severe prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) have been examined as the principal predictor of neurodevelopmental alterations, with little incorporation of lower doses or ecological contextual factors that can also impact neurodevelopment, such as socioeconomic resources (SER) or adverse childhood experiences (ACEs). Here, a novel analytical approach informed by a socio-ecological perspective was used to examine the associations between SER, PAE and/or PTE, and ACEs, and their effects on neurodevelopment.MethodsN = 313 mother-child dyads were recruited from a prospective birth cohort with maternal report of PAE and PTE, and cross-sectional structural brain neuroimaging of child acquired via 3T scanner at ages 8–11 years. In utero SER was measured by maternal education, household income, and home utility availability. The child’s ACEs were measured by self-report assisted by the researcher. PAE was grouped into early exposure (<12 weeks), continued exposure (>=12 weeks), and no exposure controls. PTE was grouped into exposed and non-exposed controls.ResultsGreater access to SER during pregnancy was associated with fewer ACEs (maternal education: β = −0.293,p = 0.01; phone access: β = −0.968,p = 0.05). PTE partially mediated the association between SER and ACEs, where greater SER reduced the likelihood of PTE, which was positively associated with ACEs (β = 1.110,p = 0.01). SER was associated with alterations in superior frontal (β = −1336.036, q = 0.046), lateral orbitofrontal (β = −513.865, q = 0.046), caudal anterior cingulate volumes (β = −222.982, q = 0.046), with access to phone negatively associated with all three brain volumes. Access to water was positively associated with superior frontal volume (β=1569.527, q = 0.013). PTE was associated with smaller volumes of lateral orbitofrontal (β = −331.000, q = 0.033) and nucleus accumbens regions (β = −34.800, q = 0.033).ConclusionResearch on neurodevelopment following community-levels of PAE and PTE should more regularly consider the ecological context to accelerate understanding of teratogenic outcomes. Further research is needed to replicate this novel conceptual approach with varying PAE and PTE patterns, to disentangle the interplay between dose, community-level and individual-level risk factors on neurodevelopment

Investigating the Impact of Prenatal Exposure to Hypertensive Disorders of Pregnancy on Adolescent Neurodevelopment and Pubertal Maturation: A Study of Neuroimaging and Salivary Biological Measures.

ABSTRACT OF DISSERTATIONInvestigating the Impact of Prenatal Exposure to Hypertensive Disorders of Pregnancy on Adolescent Neurodevelopment and Pubertal Maturation: A Study of Neuroimaging and Salivary Biological Measures. By Vida Bobela Fabiola Rebello Doctor of Philosophy in Public Health University of California, Irvine, 2023 The increasing prevalence of hypertensive disorders of pregnancy (HDP), including specific types of HDP like pregnancy-related hypertension (PR-HTN), preeclampsia, and eclampsia (P/E), pose significant health risks for pregnant individuals and their offspring. Although, prenatal HDP exposure has been reported to augment children’s sensitivity to adverse health outcomes, few studies have examined the long-term associations of prenatal exposure to HDP on neurodevelopment and hormone profiles beyond childhood. Adolescence is a critical period during which both the brain and the endocrine system undergo substantial development, representing a core risk period for when HDP-related differences may become discernable. Previous studies on the impact of HDP on adolescent health have primarily focused on discrete populations (e.g., clinical, low prevalence populations) exposed to a single type of HDP, predominantly preeclampsia. Moreover, these studies have been constrained by the lack of prospective follow-up and insufficient consideration of potential mediators. Elucidating the biophysiological mechanisms that demonstrate long-term postnatal alterations following prenatal exposure to HDP is needed. Therefore, the objective of this dissertation was to identify biological measures pertinent to psychopathology and metabolic risks influenced by HDP and to examine the role of HDP types in these relationships, utilizing the Developmental Origins of Health and Disease (DOHaD) framework. Data from the longitudinal Adolescent Brain Cognitive Development (ABCD) Study© was used, including approximately 11,888 adolescents aged 9-10 years at baseline. In Chapter 2, direct and indirect associations between HDP and cortical and subcortical brain structures were examined while accounting for the mediating role of intracranial volume in adolescents, using structural magnetic resonance imaging (sMRI) measures at two timepoints: baseline and year 2 follow-up. In chapter 3, diffusion weighted MRI (dMRI) measures were employed at two time points (baseline and Year 2 follow-up) to assess whether prenatal exposure to HDP contributes to white matter connectivity differences among the adolescents. In chapter 4, the influence of HDP on long-term endocrine development focusing in on androgen hormone profiles were investigated at three timepoints: baseline, year 1 follow-up and year 2 follow-up among the adolescents. HDP exposure was categorized as pregnancy-related hypertension (PR-HTN), preeclampsia/eclampsia (P/E), or unexposed (no HDP). Hierarchical mixed effects models were used to account for the multilevel data structure, and analyses were stratified by biological sex. In Chapter 1, findings demonstrate direct and indirect impact of prenatal exposure to HDP on the development of cortical and subcortical brain structure, identifying distinct variations in the impact of prenatal HDP exposure on neurodevelopment, with the observed associations being sex-dependent. Specifically, the unique consequences of the two distinct HDP types on brain structures differed between males and females. In chapter 2, further evidence is presented, illustrating that HDP exposure, particularly PR-HTN, is a significant predictor of alterations in white matter development. This association was observed exclusively among female adolescents, potentially because of the earlier onset of puberty-related initiation of myelination of white matter in females. Chapter 4 revealed distinct androgenic hormonal patterns in both males and female adolescents to the two types of HDP exposures. Collectively, this dissertation addresses the gap in our understanding of the unique ways in which PR-HTN and P/E influence adolescent neuroendocrine development. It underscores the importance of early monitoring and intervention for neurodevelopment and pubertal maturation to address potential pathological deviations that could lead to neuropsychiatric and metabolic disorders later in life. Additionally, this dissertation emphasizes the need to consider community-level hypertension in preconceptual health, as increased resources could benefit both the pregnant individuals and the child. Furthermore, it highlights the importance of accounting for prenatal HDP exposure when investigating adolescent neurodevelopment and pubertal maturation. Future research is warranted to elucidate the long-term disease outcomes associated with HDP

A call to leverage a health equity lens to accelerate human neuroscience research.

Investigation of health inequities tend to be examined, in human neurosciences, as biological factors at the level of the individual. In actuality, health inequities arise, due largely in part, to deep-seated structural factors. Structural inequality refers to the systemic disadvantage of one social group compared to others with whom they coexist. The term encompasses policy, law, governance, and culture and relates to race, ethnicity, gender or gender identity, class, sexual orientation, and other domains. These structural inequalities include but are not limited to social segregation, the intergenerational effects of colonialism and the consequent distribution of power and privilege. Principles to address inequities influenced by structural factors are increasingly prevalent in a subfield of the neurosciences, i.e., cultural neurosciences. Cultural neuroscience articulates the bidirectional relationship between biology and environmental contextual factors surrounding research participants. However, the operationalization of these principles may not have the intended spillover effect on the majority of human neurosciences: this limitation is the overarching focus of the present piece. Here, we provide our perspective that these principles are missing and very much needed in all human neuroscience subdisciplines to accelerate our understanding of the human brain. Furthermore, we provide an outline of two key tenets of a health equity lens necessary for achieving research equity in human neurosciences: the social determinants of health (SDoH) framework and how to deal with confounders using counterfactual thinking. We argue that these tenets should be prioritized across future human neuroscience research more generally, and doing so is a pathway to further gain an understanding of contextual background intertwined with the human brain, thus improving the rigor and inclusivity of human neuroscience research

Contextualizing the impact of prenatal alcohol and tobacco exposure on neurodevelopment in a South African birth cohort: an analysis from the socioecological perspective.

BACKGROUND: Alcohol and tobacco are known teratogens. Historically, more severe prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) have been examined as the principal predictor of neurodevelopmental alterations, with little incorporation of lower doses or ecological contextual factors that can also impact neurodevelopment, such as socioeconomic resources (SER) or adverse childhood experiences (ACEs). Here, a novel analytical approach informed by a socio-ecological perspective was used to examine the associations between SER, PAE and/or PTE, and ACEs, and their effects on neurodevelopment. METHODS: N = 313 mother-child dyads were recruited from a prospective birth cohort with maternal report of PAE and PTE, and cross-sectional structural brain neuroimaging of child acquired via 3T scanner at ages 8-11 years. In utero SER was measured by maternal education, household income, and home utility availability. The childs ACEs were measured by self-report assisted by the researcher. PAE was grouped into early exposure (<12 weeks), continued exposure (>=12 weeks), and no exposure controls. PTE was grouped into exposed and non-exposed controls. RESULTS: Greater access to SER during pregnancy was associated with fewer ACEs (maternal education: β = -0.293,p = 0.01; phone access: β = -0.968,p = 0.05). PTE partially mediated the association between SER and ACEs, where greater SER reduced the likelihood of PTE, which was positively associated with ACEs (β = 1.110,p = 0.01). SER was associated with alterations in superior frontal (β = -1336.036, q = 0.046), lateral orbitofrontal (β = -513.865, q = 0.046), caudal anterior cingulate volumes (β = -222.982, q = 0.046), with access to phone negatively associated with all three brain volumes. Access to water was positively associated with superior frontal volume (β=1569.527, q = 0.013). PTE was associated with smaller volumes of lateral orbitofrontal (β = -331.000, q = 0.033) and nucleus accumbens regions (β = -34.800, q = 0.033). CONCLUSION: Research on neurodevelopment following community-levels of PAE and PTE should more regularly consider the ecological context to accelerate understanding of teratogenic outcomes. Further research is needed to replicate this novel conceptual approach with varying PAE and PTE patterns, to disentangle the interplay between dose, community-level and individual-level risk factors on neurodevelopment

Table_1_Contextualizing the impact of prenatal alcohol and tobacco exposure on neurodevelopment in a South African birth cohort: an analysis from the socioecological perspective.DOCX

BackgroundAlcohol and tobacco are known teratogens. Historically, more severe prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) have been examined as the principal predictor of neurodevelopmental alterations, with little incorporation of lower doses or ecological contextual factors that can also impact neurodevelopment, such as socioeconomic resources (SER) or adverse childhood experiences (ACEs). Here, a novel analytical approach informed by a socio-ecological perspective was used to examine the associations between SER, PAE and/or PTE, and ACEs, and their effects on neurodevelopment.MethodsN = 313 mother-child dyads were recruited from a prospective birth cohort with maternal report of PAE and PTE, and cross-sectional structural brain neuroimaging of child acquired via 3T scanner at ages 8–11 years. In utero SER was measured by maternal education, household income, and home utility availability. The child’s ACEs were measured by self-report assisted by the researcher. PAE was grouped into early exposure (=12 weeks), and no exposure controls. PTE was grouped into exposed and non-exposed controls.ResultsGreater access to SER during pregnancy was associated with fewer ACEs (maternal education: β = −0.293,p = 0.01; phone access: β = −0.968,p = 0.05). PTE partially mediated the association between SER and ACEs, where greater SER reduced the likelihood of PTE, which was positively associated with ACEs (β = 1.110,p = 0.01). SER was associated with alterations in superior frontal (β = −1336.036, q = 0.046), lateral orbitofrontal (β = −513.865, q = 0.046), caudal anterior cingulate volumes (β = −222.982, q = 0.046), with access to phone negatively associated with all three brain volumes. Access to water was positively associated with superior frontal volume (β=1569.527, q = 0.013). PTE was associated with smaller volumes of lateral orbitofrontal (β = −331.000, q = 0.033) and nucleus accumbens regions (β = −34.800, q = 0.033).ConclusionResearch on neurodevelopment following community-levels of PAE and PTE should more regularly consider the ecological context to accelerate understanding of teratogenic outcomes. Further research is needed to replicate this novel conceptual approach with varying PAE and PTE patterns, to disentangle the interplay between dose, community-level and individual-level risk factors on neurodevelopment.</p