The role of positive affect and depressive illness in the structural development of the neural reward system during adolescence

© 2012 Dr. Meg Jayne DennisonDisturbances in positive affect are a primary feature of depressive disorders. The relationship between positive affect and depression has long been described in the personality and temperament literature, and, consistent with the definition of temperament, a biological basis for this relationship has been proposed. Over the past two decades a growing body of evidence suggests an association between neurological systems hypothesised to support the experience of positive affect, particularly the dopaminergic reward system, and depression. Interestingly, neurodevelopmental research has shown that the development of the dopaminergic system undergoes significant remodelling during adolescence, a period of life that, relative to childhood, is associated with a marked increase in risk for developing a depressive illness. These coincident effects have led researchers to postulate that brain development during this period of life may be related to both normal and abnormal changes in positive affectivity observed in adolescence; however there have been very few clear expositions of the particular mechanisms involved in determining healthy or pathological outcomes. To date there have been very few empirical investigations of the relationships between positive affect, brain development and depression. This study aimed to address this shortcoming by prospectively describing structural brain development in key subcortical regions of the dopaminergic reward system (i.e., nucleus accumbens, hippocampus, pallidum, caudate, putamen) in a group of adolescents at high and low risk (determined by childhood temperament) of developing depression. Volumetric change was the chosen variable of interest firstly because it can be meaningful described longitudinally, and secondly, because there is a gap in current knowledge about how the aforementioned structures change volumetrically during this period of life. After a review of the literature, a model was proposed that described how dysregulated positive affect might contribute to abnormal brain development in the dopaminergic reward system during adolescence. Subsequently, three key aims for this investigation were described. The first aim was to further clarify normal structural development, and it was hypothesised that all regions of interest would undergo significant volumetric change consistent with previous descriptions (Study 1). Secondly, it was hypothesised that temperamental positive affect measured prior to adolescence would predict differences in brain development in reward related regions (Study 2). Finally, it was hypothesised that the experience of depression during early to middle adolescence would be associated with deviant brain development relative to healthy controls during this period of life (Study 3), and that this pattern of development would be similar to that described for individuals with low positive affect (i.e., patterns described in Study 2). The current study longitudinally investigated a community sample from metropolitan Melbourne, Australia, of 89 adolescents at ages 12 and 16 years that were selected based on high/low risk for depressive illness. Children with a prior history of depressive illness were excluded, allowing for a prospective investigation into the onset of depression during adolescence. Structural MRI data, cognitive ability, depressive symptoms and lifetime clinical diagnoses were obtained at both assessments. Temperamental measures of positive affect were obtained at the baseline assessment. MRI imaging analysis was conducted using Freesurfer (v 4.5; longitudinal stream) to obtain subcortical brain volumes from both time points. In Study 1, the overarching hypothesis that each of the ROIs would undergo significant change was generally supported, and some novel findings regarding sex differences and hemisphere effects were observed. In Study 2, lower levels of positive affect were associated with smaller left hippocampal volumes. Developmentally, positive affect moderated development of the right hippocampus and right caudate, whereby lower levels of positive affect were associated with smaller changes in volume over time (i.e., less plasticity) relative to higher levels of positive affect. In Study 3, the experience of depressive illness in early adolescence was associated with deviant brain development, relative to healthy adolescents, in the left (both sexes) and right (females only) caudate and the left (both sexes) and right (females only) putamen. Furthermore, independent of time, depressed males had smaller left hippocampal volumes. There was some support for the hypothesis that the deviant development associated with depression was similar to that associated with temperamentally low positive affect, although the effects associated with depression were more widely distributed across the subcortical regions and moderated by sex. These findings were contextualised within the current literature and possible explanations for these findings were reviewed. It was concluded that brain development during adolescence is influenced by the experience of positive affect, and it was suggested that this might be a biological mechanism that further explains the prospective relationship between temperament and depressive illness during adolescence. Furthermore, the alterations to brain development trajectories associated with the experience of depression may act like a biological scar, which could contribute to the high risk of recurrence associated with adolescent onset depression. The finding of developmental effects, as well as the difficulty of integrating some of the findings with the existing adult and child literature from cross-sectional investigations, strongly emphasised the importance of taking a developmental perspective when studying the relationships between brain structure and depression. Finally, conceptual challenges regarding an evolving definition of positive affect (i.e., one that draws upon psychological and neurobiological perspectives), as well as clinical implications arising from this study, particularly relating to early intervention strategies targeting low positive affectivity, were discussed. Throughout the final chapter several suggestions for future research are discussed