Brain iron distribution in transdiagnostic mental health burden.

Background: Psychiatric diseases are increasingly understood as a spectrum or continuous phenomena, ranging from healthy to severely affected, yet neurobiological correlates for these dimensions remain elusive. Regional alteration of iron levels in the central nervous system may reflect neuropathological processes that result in significant impairment of cognitive and behavioral functions. The aim of this study was to characterize brain iron distribution in individuals with common clinical psychiatric disorders and offspring of individuals affected by these disorders. Methods: R2* magnetic resonance imaging (MRI) based multi-parameter mapping (MPM) algorithm was used to assess regional brain iron distribution in a) individuals diagnosed with bipolar disorder (BD), borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and offspring (n = 80, age = 23 ± 7 y., 61% females), and b) healthy controls and offspring controls (n = 43, age = 25 ± 9, 56% females). Hierarchical cluster analysis (HCA) was used to identify group-divisive patterns of regional brain iron distribution. Results: Three distinct clusters of regional brain iron distribution were found, differentiating patients and patient offspring from healthy controls and control offspring with 94% sensitivity (OR: 8.9; p = 0.038). Secondary analysis revealed no significant difference in brain iron distribution among BD, BPD, and ADHD diagnoses. Conclusion: Our finding of a characteristic brain iron distribution pattern in individuals diagnosed with BD, BPD, and ADHD and offspring of diagnosed individuals supports that brain iron patterns may serve as neurobiological correlates for psychiatric disorders conceptualized as spectrum conditions. Further, longitudinal studies are needed to confirm whether pattern analysis of brain iron distribution may represent a transdiagnostic biomarker for a better understanding of underlying neuropathology in psychiatric disorders.