The influence of parenting and genetic variants on internalising symptoms during late childhood: neural mechanisms and the HPA-axis
Document TypePhD thesis
Access StatusOpen Access
© 2019 Dr. Elena Pozzi
© 2019 Dr. Elena Pozzi
Background: Greater levels of internalising symptoms during childhood and adolescence increase the risk of developing depression later in life. As such, investigating risk factors for depression in young people is important for understanding the aetiology of the disorder and for informing prevention strategies. Whilst it is known that extreme forms of childhood adversities, such as childhood trauma and abuse, represent a risk factor for depression, less has been done in investigating the effect of parenting behaviour. Emerging research suggests that negative parenting practices (e.g., parental rejection), as well as the lack of positive parental behaviours, increase the risk of internalising symptoms during childhood and adolescence. One of the proposed mechanisms linking poor parenting practices and depression is the effect of parenting behaviour on brain function and brain structure, particularly in regions involved in processing and regulating responses to emotional stimuli, such as the amygdala, prefrontal cortex and hippocampus. Animal studies suggest that parenting may affect the brain via effects on the hypothalamic-pituitary-adrenal (HPA) axis, which has a central role in the response to stress. Genetic factors are also likely to play a role, whereby genetic variants in HPA axis genes may contribute to the regulation/dysregulation of the system. To date, however, there is a lack of research focusing on genes related to HPA axis function, and their interaction with environmental factors (including parenting) in predicting internalising symptoms. Further, no research has investigated the neural mechanisms by which parenting behaviours, HPA genes, and their interaction, exert their influence on internalising symptoms. The aim of this thesis was to investigate a) whether parenting behaviour interacts with HPA genes to influence internalising symptoms in children/adolescents, and b) whether brain structure/function of regions involved in emotion processing (particularly the amygdala and hippocampus) mediates this link. Method: Data from two longitudinal studies were used in this thesis: the Adolescent Development Study (ADS) and the Families and Childhood Transitions Study (FACTS), to explore aims across three experimental chapters. The first study included 98 adolescents from the ADS, for whom hippocampal structural development was measured from magnetic resonance imaging (MRI) scans performed across three waves (W): W1 (mean age =12.6 years), W2 (mean age=16.5 years), W3 (mean age =18.8 years). Maternal negative behaviour was measured at W1 from an observed interaction task. Adolescents’ depressive symptom severity was measured at W1 and W3 with self-reported questionnaires, and genetic risk was calculated using a composite HPA genetic risk score. The second and third studies included 86 (mean age=10.1 years) and 80 (mean age=10.0 years) children, respectively, from FACTS. Observational measures of maternal parenting behaviour were collected during mother-child interactions. Children underwent functional MRI (fMRI) while performing an implicit emotion-processing task. Self-reported and parent-reported measures of child internalising symptoms were also collected. HPA genetic risk was calculated in a similar fashion to the first study. Results: Across both studies, neither HPA genetic risk score nor the interaction between HPA genetic risk score parenting behaviour predicted internalising symptoms in children/adolescents. For study 1, we did not find support for a mediating role of hippocampal structure in the relationship between parenting behaviour and internalising symptoms. Rather, we found a moderation effect such that negative maternal parenting behaviour predicted depressive symptoms longitudinally in adolescents with flattened hippocampal growth and HPA genetic risk. While maternal behaviour was not associated with hippocampal development, in study 2 it was associated with activity/connectivity in brain regions involved in emotion processing. In particular, maternal negative behaviour during a problem-solving interaction was associated with increased amygdala reactivity and connectivity with parietal cortex in children. Maternal negative behaviour during an event-planning interaction was associated with decreased activity in the lingual gyrus in girls. Maternal communicative behaviour was associated with increased medial orbitofrontal cortex activity. These parenting-related neural findings were not associated with child internalising symptoms. In study 3, HPA genetic risk predicted increased amygdala-precuneus connectivity, which in turn was associated with greater internalising symptoms in children. Moreover, HPA genetic risk interacted with negative maternal parenting behaviour to predict increased connectivity between amygdala and superior frontal gyrus, anterior cingulate cortex and parietal cortex. Conclusion: These results suggest that there is a complex interplay between neurobiological, environmental and genetic factors in predicting internalising symptoms in children and adolescents. Neurobiological factors (e.g., hippocampal development) may act as an independent risk factor for depressive symptom severity, but they may also be influenced by environmental and genetic factors. Parenting behaviour, particularly maternal negative and communicative behaviour, may influence brain activity and connectivity in regions involved in emotion processing. The lack of association with internalising symptoms hampers our ability to draw conclusions on the significance of the parenting-related neural findings for children’s mental health. However, given that depression is characterised by impaired emotion processing, including increased sensitivity towards negative stimuli, we speculate that differences associated with negative parenting behaviour, such as amygdala heightened reactivity to negative stimuli, may represent a risk factor for the disorder. HPA genetic variants may moderate the effect of parenting behaviour on these circuits (particularly the frontoamygdala circuitry), such that not all children are sensitive to parenting effects on neurobiology, and may confer risk for depression via altering corticolimbic connectivity. This study highlights the importance of parenting behaviour for children emotional neurocircuitry development and demonstrates the moderating role of genetic factors.
Keywordsparenting; fMRI; MRI; HPA axis; genes; emotion; internalising symptoms
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