monochrome-multiplex-quantitative-pcr-telomere-length-measurement

Monochrome Multiplex Quantitative PCR Telomere Length Measurement

Telomeres are ribonucleoprotein structures at the end of all eukaryotic chromosomes that protect DNA from damage and preserve chromosome stability. ...

Boston Children’s Hospital

To examine the impact of the catechol-O-methyltransferase (COMT) val(158)met allele on depressive symptoms in young children exposed to early severe social deprivation as a result of being raised in institutions.

Modification of depression by COMT val158met polymorphism in children exposed to early severe psychosocial deprivation.

To test whether genotype of the serotonin transporter-linked polymorphic region (5HTTLPR) and atypical attachment interact to predict externalizing psychopathology prospectively in a sample of children with a history of early institutional care.

Serotonin Transporter Genotype (5HTTLPR) Moderates the Longitudinal Impact of Atypical Attachment on Externalizing Behavior.

Early social deprivation can negatively affect domains of functioning. We examined psychopathology at age 12 years in a cohort of Romanian children who had been abandoned at birth and placed into institutional care, then assigned either to be placed in foster care or to care as usual.

Effects of institutional rearing and foster care on psychopathology at age 12 years in Romania: follow-up of an open, randomised controlled trial.

Genome-wide association studies have identified allelic variation in CACNA1C as a risk factor for multiple psychiatric disorders associated with limbic system dysfunction, including bipolar disorder, schizophrenia, and depression. The CACNA1C gene codes for a subunit of L-type voltage-gated calcium channels, which modulate amygdala function. Although CACNA1C genotype appears to be associated with amygdala morphology and function in adults with and without psychopathology, whether genetic variation influences amygdala structure and function earlier in development has not been examined.

Variation in CACNA1C is Associated with Amygdala Structure and Function in Adolescents.

Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the proportion of time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4.

DNA methylation at stress-related genes is associated with exposure to early life institutionalization.

Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2-4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child's life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening.

Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level.

To determine the effects of foster care vs institutional care, as well as disruptions in the caregiving environment on physical development through early adolescence.

Caregiving Disruptions Affect Growth and Pubertal Development in Early Adolescence in Institutionalized and Fostered Romanian Children: A Randomized Clinical Trial.

Telomere length (TL) has been linked to several psychiatric conditions in children and adults. Telomere shortening is accelerated by early adversity, including maltreatment and psychosocial deprivation. These experiences also increase the risk of psychopathology in many domains. Two fundamental issues remain unresolved. The first concerns the specificity of the relations between TL and different dimensions of psychopathology; and the second relates to the direction of association between TL and psychopathology.

Telomere Length and Psychopathology: Specificity and Direction of Effects Within the Bucharest Early Intervention Project.

Pregnancy can exacerbate or prompt the onset of stress-related disorders, such as post-traumatic stress disorder (PTSD). PTSD is associated with heightened stress responsivity and emotional dysregulation, as well as increased risk of chronic disorders and mortality. Further, maternal PTSD is associated with gestational epigenetic age acceleration in newborns, implicating the prenatal period as a developmental time period for the transmission of effects across generations. Here, we evaluated the associations between PTSD symptoms, maternal epigenetic age acceleration, and infant gestational epigenetic age acceleration in 89 maternal-neonatal dyads. Trauma-related experiences and PTSD symptoms in mothers were assessed during the third trimester of pregnancy. The MethylationEPIC array was used to generate DNA methylation data from maternal and neonatal saliva samples collected within 24 h of infant birth. Maternal epigenetic age acceleration was calculated using Horvath's multi-tissue clock, PhenoAge and GrimAge. Gestational epigenetic age was estimated using the Haftorn clock. Maternal cumulative past-year stress (GrimAge:  = 3.23e-04, PhenoAge:  = 9.92e-03), PTSD symptoms (GrimAge:  = 0.019), and difficulties in emotion regulation (GrimAge:  = 0.028) were associated with accelerated epigenetic age in mothers. Maternal PTSD symptoms were associated with lower gestational epigenetic age acceleration in neonates ( = 0.032). Overall, our results suggest that maternal cumulative past-year stress exposure and trauma-related symptoms may increase the risk for age-related problems in mothers and developmental problems in their newborns.

Cumulative stress, PTSD, and emotion dysregulation during pregnancy and epigenetic age acceleration in Hispanic mothers and their newborn infants.

Exposure to stress related to the COVID-19 pandemic contributes to psychopathology risk, yet not all children are negatively impacted. The current study examined a parasympathetic biomarker of stress sensitivity, respiratory sinus arrhythmia (RSA), as a moderator of the effects of exposure to pandemic stress on child internalizing and externalizing behaviors in a sample of children experiencing economic marginalization. Three to five years pre-pandemic, when children were preschool-aged, RSA during baseline and a challenging parent-child interaction were collected. Mid-pandemic, between November 2020 and March 2021, children's exposure to pandemic stress and internalizing and externalizing behaviors were collected. Results demonstrated that children who, pre-pandemic, demonstrated blunted parasympathetic reactivity (i.e., no change in RSA relative to baseline) during the dyadic challenge exhibited elevated risk for externalizing behaviors mid-pandemic. Further, this risk was greatest for children exposed to high and moderate levels of pandemic stress. Consistent with diathesis stress and polyvagal frameworks, these conditional effects suggest that blunted parasympathetic reactivity in response to stress in early childhood may escalate the development of externalizing behaviors following stress exposure at school age.

Pre-COVID respiratory sinus arrhythmia moderates associations between COVID-19 stress and child externalizing behaviors: Testing neurobiological stress theories.

Article	Year
Modification of depression by COMT val158met polymorphism in children exposed to early severe psychosocial deprivation. Child abuse & neglect\| PubMed ID: 20403637	2010
Serotonin Transporter Genotype (5HTTLPR) Moderates the Longitudinal Impact of Atypical Attachment on Externalizing Behavior. Journal of developmental and behavioral pediatrics : JDBP\| PubMed ID: 25933228	2015
Effects of institutional rearing and foster care on psychopathology at age 12 years in Romania: follow-up of an open, randomised controlled trial. The lancet. Psychiatry\| PubMed ID: 26303560	2015
Variation in CACNA1C is Associated with Amygdala Structure and Function in Adolescents. Journal of child and adolescent psychopharmacology\| PubMed ID: 26401721	2015
DNA methylation at stress-related genes is associated with exposure to early life institutionalization. American journal of physical anthropology\| PubMed ID: 27218411	2016
Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level. Psychiatry research\| PubMed ID: 27677058	2016
Caregiving Disruptions Affect Growth and Pubertal Development in Early Adolescence in Institutionalized and Fostered Romanian Children: A Randomized Clinical Trial. The Journal of pediatrics\| PubMed ID: 30172435	2018
Telomere Length and Psychopathology: Specificity and Direction of Effects Within the Bucharest Early Intervention Project. Journal of the American Academy of Child and Adolescent Psychiatry\| PubMed ID: 30844465	2020
Cumulative stress, PTSD, and emotion dysregulation during pregnancy and epigenetic age acceleration in Hispanic mothers and their newborn infants. Epigenetics\| PubMed ID: 37433036	2023
Pre-COVID respiratory sinus arrhythmia moderates associations between COVID-19 stress and child externalizing behaviors: Testing neurobiological stress theories. Development and psychopathology\| PubMed ID: 38273710	2024

Stacy S. Drury

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