Adversity and Resilience, Postpartum Depression, Suicide, and Racial/Ethnic Disparities

Perinatal depression, which can involve prenatal or postnatal depression, is common and when severe can have dire consequences for mother, baby, and family. It is interesting that data suggest that perinatal depression is more heritable than non-perinatal depression (2). Guintivano and numerous co-authors (3) present data from a meta-analysis of GWAS data collected from 18,770 women with PPD and 58,461 control subjects to better understand the genetic underpinnings of PPD. The sample included 20 cohorts, 18 of which consisted of individuals of European descent. The two additional cohorts, with considerably fewer individuals, were made up of 975 women with PPD of East Asian ancestry and 456 PPD women of African ancestry, respectively. In relation to interpretation of the data, it should be noted that the PPD participants could have had other prior psychiatric illnesses, including major depression or bipolar depression. Although this is the largest GWAS of PPD patients examined to date, the sample is still relatively small and, not surprisingly, none of the findings passed standard GWAS statistical corrections (p<5x10^-8). In the analysis only with data from women of European ancestry, the researchers found evidence for polygenicity that explained about 14% of the total heritability. A total of 62 SNPs were identified that were associated with PPD. The most significant SNP was located in the thioredoxin reductase 2 gene (TXNRD2), which encodes for a mitochondrial protein involved in metabolism. When including the smaller numbers of PPD participants of African and East Asian ancestry in the analysis, the total amount of heritability accounted for by the SNPs increased to 16%. In this analysis, the most significant SNP found to be associated with PPD was in the fibroblast growth factor receptor substrate 2 gene (FRS2), which encodes a protein that facilitates the activity of various neurotrophic factor receptors. Genetic correlations were performed to understand the extent to which PPD shares genetic underpinnings with other disorders. These analyses revealed extremely high genetic correlations with major depression, high correlations with anxiety disorders (especially PTSD), a moderate correlation with bipolar II disorder, and a smaller correlation with bipolar I disorder. The researchers also found genetic correlations with insomnia and polycystic ovary syndrome. Finally, the researchers used other gene expression data sets to understand the brain regions and cell types that are enriched for the expression of the genes that were identified to be associated with PPD. Based on this analysis, findings pointed to the possibility of involvement of GABA-related inhibitory neurons in the thalamus and cholinergic neurons in the hypothalamus. In their editorial (4), Jessica Adams and Dr. Divya Mehta from Queensland University of Technology along with Dr. Prabha Chandra from the National Institute of Mental Health and Neuroscience in Bangalore, India, further discuss these findings and their implications.

Breslow et al. (5) use self-report data from 992 health care workers from the Montefiore Health System in the Bronx, New York, to characterize potential disparities related to race and ethnicity in experiencing COVID-19 related stress, levels of distress, and psychiatric symptoms. The data used was collected online over an approximately 8-month period from April 2020 to the end of January 2021. Primary measures of stressor outcomes included redeployment to another area of the health care system, fear of contracting COVID-19, a positive COVID-19 test, lack of autonomy at work, and lack of access to personal protective equipment. The distress-related primary outcomes were evaluated with the Impact of Event Scale, which asked questions relevant to the cognitive, emotional, and behavioral consequences of dealing with the pandemic. Additionally, exploratory analyses were performed to understand COVID-19 related psychiatric symptoms. The racial and the ethnic composition of the sample was 52% White, 14% Latinx/Hispanic, 11% Black/African American, 17% Asian/Asian American, and 7% multi/biracial, or other. Before summarizing the results, it is important to emphasize that the authors did not correct for multiple comparisons in their analyses using the rationale that they did not want to miss any potentially important racial/ethnicity findings. In general, Latinx, Black, Asian, and Multiracial/Other individuals reported significantly higher levels of experiencing COVID-related stressors. Compared to White participants, the Latinx individuals were the only group to have reported a significantly increased prevalence of distress (30% vs. 45%). Additionally, the relation between increased levels of stress and the reported levels of distress did not significantly differ across the racial/ethnic groups. Finally, regarding psychiatric symptoms, Latinx participants had a significantly higher prevalence of PTSD compared to White participants and White participants had a greater prevalence of moderate to severe anxiety symptoms compared to Asian participants. Furthermore, compared to all other groups, White participants reported significantly greater hazardous alcohol use (53% vs. 20%–30%). In their Editorial, Drs. Rachel Yehuda and Sidney Hankerson from the Icahn School of Medicine at Mount Sinai (6) provide an in-depth discussion of this study, highlighting the multifaceted issues that should be considered when studying the impacts of structural racism on mental health.

Copeland and colleagues (7) use data from a large cohort from the Great Smoky Mountain Study to assess the relation between early adversity and the development of psychiatric illnesses during adolescence and early adulthood. The data from this unique sample affords the opportunity to longitudinally characterize this relation and to better understand the extent to which children exposed to adversity do, and do not, develop psychiatric disorders. Of particular interest, and relevant to how we conceptualize resilience, are the adult follow-up data on the children that were deemed to have significant childhood risk. Data from 1,420 participants were used for the analyses, and assessment of adversities and psychiatric illnesses were performed up to eight times between 9–16 years of age. Additionally, data were collected from participants when they were 25- and 30-years old to characterize psychiatric diagnoses and other measures related to health, achievement, and functioning. Childhood adversities included the following categories: low socioeconomic status, unstable family structure, family dysfunction, maltreatment, and peer victimization. Results demonstrated that during childhood approximately 65% of the participants had a psychiatric diagnosis or significant subthreshold symptoms. Exposure to childhood adversity markedly increased the likelihood of developing a childhood psychiatric disorder. This effect was cumulative as each additional type of adversity that was experienced increased the relative risk of developing a disorder by approximately 1.7 times. Low-risk children were defined as children exposed to one or no childhood adversities, whereas risk children had to have been exposed to two or more of the adversity domains. When considering resilience, the authors focused on the 650 children in the risk group, designating the resilient group to be those 63 individuals that did not develop a childhood psychiatric disorder. However, when assessed at 25 and 30 years of age, compared with low-risk children, these so-called “resilient children” had a significantly greater likelihood of developing anxiety and depressive disorders but not substance use disorders. Compared with low-risk individuals, those in the resilient group were also more likely to have poorer physical health as well as worse financial and educational achievement. When compared with participants who had childhood psychiatric illnesses, as adults the resilient group did better in relation to physical health and social functioning. These findings point to the marked impact of early-life adversity on mental health and functional outcomes, even in children who initially appear to be relatively unaffected. In their editorial (8), Dr. Brent Roberts and Cavan Bonner from the University of Illinois at Urbana-Champaign focus on the findings in relation to the more pervasive effects of experiencing trauma and provide a nuanced discussion of what types and intensity of stressors may or may not lead to psychological growth, which could promote resilience.

Black girls and women face considerable stressors that contribute to their risk to develop psychiatric illnesses, as well as to engage in suicidal behaviors. From the standpoint of stress and factors contributing to risk, the impacts of structural racism on mental health cannot be overestimated. A priority data letter by Joseph and colleagues (9) focuses on understanding suicide rates in Black girls and women. By using 1999–2020 National Center for Health Statistics’ Multiple Cause of Death data, the authors characterized the incidence and trends in suicide that occurred in 15–84-year-old Black female individuals. Findings demonstrated an overall increase in the rate of suicides, with the most dramatic increases occurring during adolescence into early adulthood. Specifically, the suicide rate in Black female individuals across all ages increased from 2.1/100,000 to 3.4/100,000 from 1999 to 2020, and across the United States the greatest increases occurred in the West. It is notable that in the 15–24 age group, the suicide rate increased very dramatically, from 1.9/100,000 to 4.9/100,000. Additionally, the highest suicide rates occurred in individuals who were born after 2002. These data not only demonstrate the increasing risk of suicide faced by Black girls and women but highlight that the greatest increases are occurring in younger Black female individuals. In their editorial (10), Dr. Ruth Shim from the University of California at Davis and Dr. Carolyn Rodriguez from Stanford University discuss the findings in this paper while emphasizing the impact of structural racism and intersectionality on Black female individuals. Importantly, they enumerate strategies that can be invoked to mitigate the effects of these stressors on the mental health of Black girls and women.

Stress, trauma, and adversity are prominent factors that predispose vulnerable individuals to the development and exacerbation of psychiatric illnesses. Why one individual might be more vulnerable, and another more resilient, to adversity clearly involves one’s genetic endowment as it interacts with prior experiences related to environment, stress, and coping. The papers in this issue of the Journal incorporate the themes of adversity, resilience, and genetics to shed new light on our understanding of postpartum depression, suicide, responses to stress in adulthood, and adversity in children. It is important to note that two papers in this issue deal with the negative impacts of structural racism and the stress associated with belonging to racial and ethnic minority groups. The major takeaway points from studies in this issue include 1) new leads involving genetic alterations associated with the risk to develop postpartum depression; 2) higher levels of stress experienced by racial and ethnic minority health care workers during COVID-19; 3) how children exposed to early-life adversity who appeared to have been resilient during childhood have an increased adult risk of developing anxiety and depressive disorders; and 4) suicide rates have increased in Black girls and women, with the most dramatic increases occurring in adolescents and young adults.