Melbourne School of Population and Global Health - Research Publications
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ItemSometimes It's Good to be Short: The Serotonin Transporter Gene, Positive Parenting, and Adolescent Depression(WILEY, 2019-07)In threatening environments, the short (S) allele of 5-HTTLPR is proposed to augment risk for depression. However, it is unknown whether 5-HTTLPR variation increases risk for depression in environments of deprivation, lacking positive or nurturant features. Two independent longitudinal studies (n = 681 and 176, respectively) examined whether 5-HTTLPR moderated associations between low levels of positive parenting at 11-13 years and subsequent depression at 17-19 years. In both studies only LL homozygous adolescents were at greater risk for depression with decreasing levels of positive parenting. Thus, while the S allele has previously been identified as a susceptible genotype, these findings suggest that the L allele may also confer sensitivity to depression in the face of specific environmental challenges.
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ItemAssociation between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: a longitudinal prospective study(SPRINGERNATURE, 2014-09)The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD) between age 13-19 years, in a longitudinal study of 174 adolescents (48% males). Increasing copies of S-alleles were found to predict smaller left hippocampal volume, which in turn was associated with increased risk of experiencing a first onset of MDD. Increasing copies of S-alleles also predicted both smaller left and right medial OFC volumes, although neither left nor right medial OFC volumes were prospectively associated with a first episode of MDD during adolescence. The findings therefore suggest that structural abnormalities in the left hippocampus may be present prior to the onset of depression during adolescence and may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness. 5-HTTLPR genotype may also impact upon other regions of the brain, such as the OFC, but structural differences in these regions in early adolescence may not necessarily alter the risk for onset of depression during later adolescence.
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ItemLinking the Serotonin Transporter Gene, Family Environments, Hippocampal Volume and Depression Onset: A Prospective Imaging Gene X Environment Analysis(AMER PSYCHOLOGICAL ASSOC, 2015-11)A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume.