Timothy Oberlander

Professor

Relevant Degree Programs

 

Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - Nov 2019)
Functional connectivity supporting emotion perception, and resting state networks in typically developing neonates and following prenatal exposure to maternal mood disturbances and SSRIs (2019)

The first year of life is a period of dramatic structural changes in the brain. Along with structural changes, infants achieve significant behavioral milestones. The bridge between brain structure and behavior is strongly based on functional connections that enable intrinsic functioning and also develop emotion perception skills, both critical for early development. However, little is known about how these connections are functionally organized in infancy. Prenatal exposures to maternal mood disturbances and the use of selective serotonin reuptake inhibitor (SSRI) antidepressants play a crucial role in shaping infants’ development, although it remains unclear how these exposures are linked to infant developmental outcomes. In this thesis, I use task-based electroencephalography (EEG) and resting-state functional magnetic resonance imaging (rs-fMRI) combined with graph theory analysis to study the functional networks of emotion perception and the intrinsic functional connectivity of resting state networks (RSNs) in typically developing infants and in infants prenatally exposed to mood disturbances and SSRIs. I found that 8-to-10-month-old infants have network characteristics that are similar to adults when observing basic emotions (Chapter 3). Moreover, an increase in prenatal maternal mood symptoms was associated with reduced modularity only for negative emotions, while prenatal SSRI drug-exposure was associated with higher network modularity in observing both positive and negative emotions. In contrast, higher postnatal mood symptoms were associated with alterations in frontal hubs (Chapter 5). Prenatal mood disturbances were associated with alterations in intrinsic RSNs. Specifically, compared to the control group, infants exposed to prenatal maternal depression showed higher hub values of the left anterior-cingulate, insula, and caudate as well as higher hub values in the amygdala (Chapter 7). Prenatal SSRI exposure associated both with higher hub values in Heschel’s gyrus (Chapter 7) and with hyperconnectivity of the putative auditory network (Chapter 6) possibly support shifts in language perception previously reported in infants exposed to prenatal SSRI. Collectively, these data indicate that the core functional organization for observing basic emotions is in place at 8-to-10 months of age. Further, maternal mood disturbances and SSRI exposure may differently shape early intrinsic and emotion perception functional organization, possibly leading to different developmental trajectories.

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The impact of maternal depression and prenatal antidepressant exposure on child development : consideration of internal and external contextual factors (2019)

One in five women experience a depressive episode during pregnancy, with up to one in ten being treated with antidepressants. Despite an overall adverse developmental effect related to exposure to maternal depression and antidepressants during pregnancy, not all children are equally affected. Moreover, critical yet unanswered questions remain regarding the potential developmental risks and benefits of antidepressant treatment during pregnancy. The purpose of this thesis was to study the association between maternal depression and prenatal antidepressant exposure and child developmental outcomes while considering the role of key contextual factors that may influence these associations. Depression severity, patterns of depressive symptoms over time, and underlying genetic risk were investigated for their role in influencing child outcomes. Small yet consistent associations were found between prenatal antidepressant exposure and vulnerability for anxiety and lower physical independence at kindergarten age, after stringently adjusting for confounding by maternal mental health. Genetic differences were found to underlay associations between prenatal maternal depression symptom levels and genome-wide differences in DNA methylation at age 18 years. Looking longitudinally, increasing maternal depression symptoms across the first three postpartum years were associated with worse child behavioral problems and executive functions at ages three and six years; a pattern of decreasing maternal depression symptoms over the same time period, despite initially higher depressive symptoms during pregnancy, was associated with no impairments.Collectively, the findings presented herein help explain the heterogeneity of child outcomes that are observed in relation to early developmental exposure to maternal depression and its treatment with antidepressants. This thesis highlights the impact of factors underlying and related to maternal mental health on children’s developmental outcomes, and suggest that investments made to improve maternal depression have the potential to benefit the health of both mothers and their children.

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Master's Student Supervision (2010 - 2018)
Programming of stress regulation in 5 - 7 year old children by maternal gestational mood and antidepressant use (2014)

Of particular importance to mental health across the life span is our capacity to regulate neuroendocrine responses to stressful events via the hypothalamic pituitary adrenal (HPA) axis. Prenatal exposure to maternal depression/anxiety may be among the earliest adverse experiences shown to influence the developing HPA system, possibly via changes in fetal serotonergic signaling. In addition, the developmental impact of prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants is often undistinguishable from prenatal maternal mood. The molecular mechanisms underlying how serotonin (5-HT) influences the development of the HPA stress system remain unclear, but may involve epigenetic mechanisms such as DNA methylation. This thesis explored whether prenatal exposure to SRIs and maternal depressed/anxious mood are associated with altered HPA stress reactivity, characterized by variable basal and stress-induced cortisol concentrations in 5 - 7 year-old children. Furthermore, the methylation status in promoter regions of NR3C1 1F (encodes the glucocorticoid receptor) and SLC6A4 (encodes the serotonin transporter) at birth and at 5 - 7 years of age was evaluated and the relationship to children’s cortisol patterns was assessed. Prenatal exposure to SRIs and higher 3rd trimester maternal depressed/anxious mood were associated with reduced cortisol stress responses at 5 - 7 years. Higher NR3C1 1F methylation at 5 - 7 years was associated with higher diurnal cortisol concentrations and a reduced cortisol stress response. Children exposed to mothers with higher 3rd trimester and concurrent anxious mood exhibited lower SLC6A4 methylation, compared to children exposed to higher 3rd trimester maternal anxious mood alone. Furthermore, children with higher SLC6A4 methylation at birth exhibited a reduced cortisol stress response. These findings suggest that the relationship between early life experiences and altered stress responses in early childhood may be moderated by epigenetic mechanisms involving the serotonergic and HPA regulatory systems. In addition, an interactive relationship between pre- and postnatal maternal mood with cortisol stress responses and methylation status at 5 - 7 years suggests that an early adverse environment may confer sensitivity toward altered HPA activity and regulation, and that the postnatal environment may shift the HPA stress response towards vulnerability or resilience to stress-related disorders across the lifespan.

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