Research Spotlights December 2019

Research Spotlights December 2019

Cord blood measures may predict children's social and emotional development

A recent study supported by the NIMH indicates that there is a link between fetal lipid levels (umbilical cord blood) and psychological health in children. The fetal environment has been implicated in later psychological health in previous studies. For example, maternal exposures to lead, alcohol, folate deficiency, chronic stress, and infection during gestation have all been linked to negative psychological outcomes in children. Markers for lipids, including cholesterol and triglycerides, have been used as reliable predictors of physical health. These lipid biomarkers can be categorized as high-density lipoproteins (HDLs), which are considered protect against health risk and low-density lipoproteins or very-low-density lipoproteins (VLDLs) that are associated with increased health risks. Recent research in adults has indicated a relationship between lipids and several psychological phenomena. However, it is unknown if low fetal levels of HDLs or high levels of LDLs, VLDLs, or triglycerides also have enduring effects on psychological health.

In the current study, researchers leveraged the Born in Bradford (BiB) birth cohort to examine if lipid markers predict social and emotional development. The BiB is a large, ongoing, multi-wave cohort study, which recruited pregnant women between 26 and 28 weeks of gestation from March 2007 and December 2010. Pertinent to this study the following variables were included: demographic factors, maternal depressive symptoms, prenatal vitamins use, and medical health records of the mother during pregnancy; umbilical cord blood collected at the birth of the child; general physical health of the child, as rated by the mother when the child was 3 years of age; the child’s psychosocial competences, as rated by teachers at the end of their first year of school; and the child’s BMI relative to the British population at approximately 5 years old. The study included 1,369 children (52% male) and their mothers.

Results of this study indicated that a less healthy fetal lipid profile (low levels of HDL, high levels of VLDL, and high levels of triglycerides) is associated with deficits later in childhood in the domains of emotion regulation, self-awareness, and interpersonal functioning. These results were independent of the mothers’ psychological or physical health, children’s physical health, or children’s special education status and were consistent across ethnic groups and gender. These results identify fetal exposure to anomalous lipid levels as a possible contributor to subsequent psychological health and social functioning. Further studies are needed to understand the mechanisms underlying these associations. That levels of HDL, VLDL, and triglycerides at birth were significantly related to psychosocial functioning 5 years later attests to the enduring effects of the fetal period on psychological health and suggests that lipid levels may be novel mechanisms that should be considered in the context of understanding children’s psychological functioning.

Citation:
Manczak EM, Gotlib IH, 2019. Lipid Profiles at Birth Predict Teacher-Rated Child Emotional and Social Development 5 Years Later. 2019. Psychol Sci. doi: 10.1177/0956797619885649.

Puberty may hold the key to resetting stress responses after early life adversity

Puberty may offer a window of opportunity to recalibrate the stress response of children who experienced early life adversity, according to recently published research supported by the NICHD, NIMH, and the National Science Foundation. Children that have experienced insufficient social, emotional and physical support early in life, such as those formerly in institutional (e.g., orphanage) care, often exhibit developmental delays and a blunted response of the stress hormone, cortisol. The hypothalamic–pituitary–adrenocortical (HPA) axis in the brain is responsible for this stress response and calibrates the response based on the harshness of the environment during a sensitive period in infancy. This blunted stress response is long-lasting and has been associated with negative psychological effects, even when the child is moved into an enriched and supportive environment. In this study the researcher examined whether puberty provides an opportunity to recalibrate the HPA axis toward more typical reactivity when children move from harsh deprived conditions in infancy into supportive conditions in childhood and adolescence.

This longitudinal study included 299 participants;129 participants (68.2% female) were previously institutionalized as infants or toddlers and later adopted into well-resourced and supportive homes and 170 control participants (52,4% female) that were born and raised by their natal families. Each participant completed 3 annual sessions starting from age 7 to 15, across two consecutive years, to determine pubertal stage and cortisol reactivity to the Trier social stress test for children, a stress task involving performing a speech and mental arithmetic while being filmed and evaluated.

Using a linear mixed-effects model to control for sex and between-individual differences in pubertal stage, results showed that post institutionalized participants had significant increases in cortisol reactivity as they advanced through puberty, bringing their stress responses equivalent with those experienced by the non-adopted participants. Unlike the post institutionalized participants, the non-adopted participants showed no significant differences in cortisol reactivity at any pubertal stage. These results indicate that puberty may provide an opportunity for the HPA axis to recalibrate based on the current more positive environment relative to that in infancy. Future research is needed to determine if HPA-axis recalibration impacts physical and psychological health and the exact mechanisms underlying these effects. These findings suggest that puberty may provide an opportunity for intervention with high-risk kids to support healthier life trajectories through recalibration of stress responses.

Citation:
Gunnar MR, DePasquale CE, Reid BM, Donzella B, 2019. Pubertal stress recalibration reverses the effects of early life stress in post institutionalized children. Proc Natl Acad Sci USA. 116(48):23984-23988. doi: 10.1073/pnas.1909699116.

Improving psychosis-risk detection in people with schizophrenia

Schizophrenia is a chronic and disabling disorder affecting about 1% of adolescents and young adults. In a recent publication, researchers funded by the NIMH found that using a polygenic risk score (PRS), based on data from genome-wide association studies (GWAS), improves psychosis risk prediction in high-risk individuals. In schizophrenia, genetic risk was typically determined by a family history of psychosis; however, many who develop schizophrenia do not have a family history of the disorder. GWAS have identified many common genetic variants that are associated with an increased risk of schizophrenia, which has helped with the development of PRS for schizophrenia. By incorporating genetic risk into existing psychosis risk prediction models, the researchers’ goal was to further improve the accuracy of psychosis risk-prediction in high-risk individuals.

The North American Prodrome Longitudinal Study, phase 2, is a two-year, eight-site study of predictors and mechanisms of conversion to psychosis that included 764 high-risk and 279 unaffected comparison subjects. Research criteria for a clinical high-risk syndrome identifies individuals with a 15-25% 2-year risk of psychosis. Raters used the Structured Interview for Psychosis-Risk Syndromes to determine whether indiviuals met the criteria for psychosis-risk states. Follow-ups occurred at 6-month intervals, and the date of conversion was estimated by clinical interview and/or medical records.

The PRS was based on the latest schizophrenia and bipolar GWAS. Variables in the psychosis risk calculator included stressful life events, trauma, disordered thought content, verbal learning, information processing speed, and family history of psychosis.

The results of the study showed that PRS varied significantly in individuals with European ancestry and was higher in individuals that converted to having psychosis when compared with both the nonconverter and unaffected groups. Additionally, the PRS was correlated with risk calculator variables of information processing speed and verbal memory. For non-Europeans, the PRS varied but the difference between the converters and nonconverters was not significant.

Building upon previous GWAS that developed a PRS that differentiates individuals with schizophrenia from those without schizophrenia, this study found that the PRS improves psychosis risk prediction by further differentiating individuals meeting clinical high-risk criteria and improving individualized risk assessments. The schizophrenia PRS shows promise in enhancing risk prediction in persons at high risk for psychosis, however, the potential utility will likely be limited to those of European ancestry, since it performed poorly in non-European ancestry individuals. This is likely because the PRS was developed in populations that had predominately European ancestry. Future work is needed to include non-Europeans in genetic risk studies.

Citation:
Perkins DO, Olde Loohuis L, Barbee J, Ford J, Jeffries CD, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, McGlashan TH, Seidman LJ, Tsuang M, Walker EF, Woods SW. 2019. Polygenic Risk Score Contribution to Psychosis Prediction in a Target Population of Persons at Clinical High Risk. Am J Psychiatry. doi: 10.1176/appi.ajp.2019.18060721.

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