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    Mood and anxiety outcomes in adolescents born with extremely low birthweight or extremely preterm: prevalence and neuroanatomy
    Burnett, Alice Claudia ( 2012)
    Preterm birth is associated with poor outcome in a range of domains, which can persist into adolescence and beyond. This may include poor mental health outcomes, and particularly, anxiety and depressive symptoms. To date, studies of mood and anxiety outcomes in preterm groups have mainly used dimensional measures of symptoms; only a handful employ clinical diagnostic instruments and these largely focus on recent symptoms. Our understanding of the prevalence of clinically diagnosable disorders is consequently limited, particularly in late adolescence and for those born since 1990. Prematurity at birth can also have a significant and longstanding impact on brain development. An extended medial network, including the hippocampus, amygdala, and medial prefrontal cortex, is implicated in emotion regulation, as well as clinical mood and anxiety disorders. Hippocampus, amygdala, and prefrontal structure may be altered in preterm samples, but potential relationships between these brain regions and emotional outcomes are yet to be explored in preterm survivors. This study aimed to address these limitations in the current literature by i) characterising mood and anxiety outcomes in adolescents born extremely low birthweight or extremely preterm (ELBW/EP), ii) characterising the structure of regions in the extended medial network, and iii) investigating the relationships between these outcomes and brain structure. A number of specific hypotheses arose from this research question. Firstly, it was expected that the ELBW/EP group would report more recent symptoms, more frequently meet diagnostic criteria for current or past disorder, and more strongly endorse personality traits associated with anxiety and depression than a normal birthweight (>2500g; NBW), full-term (>36 weeks; FT) control group. Secondly, it was expected that ELBW/EP participants may have smaller hippocampus, amygdala, and ventromedial prefrontal cortex volumes, and thinner ventromedial prefrontal cortices, than NBW participants. Finally, it was predicted that structural reductions in these regions of interest would be associated with greater mood and anxiety symptoms, and a history of clinically diagnosable disorder, in ELBW/EP and NBW participants. This study assessed 215 ELBW/EP and 157 NBW adolescents who were born in 1991 and 1992 in the state of Victoria, Australia. Participants from a prospective geographical cohort were followed up at age 18 and completed measures of mood and anxiety symptoms and disorders (including questionnaires and a structured clinical interview), as well as personality traits. Participants also underwent structural MRI scanning, and cortical and subcortical brain volumes were generated using FreeSurfer (v5.0). Unexpectedly, there was no elevation in clinically relevant recent or lifetime history of depression or anxiety in the ELBW/EP group. Although mood and anxiety disorders were more prevalent in females overall, there was no interaction between group and gender. The ELBW/EP group had disproportionately smaller bilateral hippocampus volumes and left amygdala volumes than controls, and the ventromedial prefrontal cortex was proportionately larger and thicker in the ELBW/EP group than the NBW group. Recent mood and anxiety symptoms were not well predicted by any of the neuroanatomical variables of interest. Despite this, lifetime history of a mood or anxiety disorder was associated with smaller left vmPFC volumes. Further analyses indicated this pattern was apparent in those with a history of anxiety disorder but not mood disorder. Group did not moderate these findings. Assessment of ELBW/EP adolescents’ self-reported mood and anxiety outcomes revealed an encouraging picture. Although extremely low birthweight or extreme prematurity was associated with altered structure of regions in the extended medial network, these alterations appeared to have limited relationship with outcomes. These findings contribute to the literature by examining older adolescent mood and anxiety outcomes and using high field-strength neuroimaging. The implications for preterm survivors and the relevance of brain structure to mood and anxiety outcomes in this age group are considered.