Abstract

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain ageing. Currently, it remains unclear whether young individuals show differential brain structure ageing trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well ( β = -0.60, p corrected < 0.001) and HR-well ( β = -0.36, p corrected = 0.02), with a potential intermediate trajectory for HR-well ( β = -0.24 years, p corrected = 0.06). Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure ageing trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

Highlights

  • Mood disorders are amongst the most common psychiatric disorders, with a life-time prevalence of around 15% (Kessler and Bromet, 2013)

  • It is known that mood disorders are highly heritable and share complex genetic architecture; individuals with a family history of Bipolar Disorder (BD) have >10-fold increased risk of developing BD or Major Depressive Disorder (MDD) (Smoller and Finn, 2003)

  • There were no significant differences between groups with regard to age at either timepoint, and no differences in gender, handedness and National Adult Reading Test (NART) intelligence quotient score

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Summary

Introduction

Mood disorders are amongst the most common psychiatric disorders, with a life-time prevalence of around 15% (Kessler and Bromet, 2013) They are the greatest contributor to non-fatal ill-health (World Health Organization, 2017). Mood disorders often manifest during adolescence and young adulthood (De Girolamo et al, 2012) During these life stages, age-related changes in brain structure contribute to cognitive development and increase vulnerability to mental illness, including mood disorders (Andersen, 2003; Dahl, 2004). Mood disorder onset may be related to changes in trajectory of brain structure development. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with differential aging trajectories, or accelerated brain ageing It remains unclear whether young individuals show differential brain structure ageing trajectories associated with onset of mood disorder and/or presence of familial risk.

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