Abstract
Adolescence is a time period associated with marked brain maturation that coincides with an enhanced risk for onset of psychiatric disorder. White matter tract myelination, a process that continues to unfold throughout adolescence, is reported to be abnormal in several psychiatric disorders. Here, we ask whether psychiatric vulnerability is linked to aberrant developmental myelination trajectories. We assessed a marker of myelin maturation, using magnetisation transfer (MT) imaging, in 10 major white matter tracts. We then investigated its relationship to the expression of a general psychopathology “p‐factor” in a longitudinal analysis of 293 healthy participants between the ages of 14 and 24. We observed significant longitudinal MT increase across the full age spectrum in anterior thalamic radiation, hippocampal cingulum, dorsal cingulum and superior longitudinal fasciculus. MT increase in the inferior fronto‐occipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus was pronounced in younger participants but levelled off during the transition into young adulthood. Crucially, longitudinal MT increase in dorsal cingulum and uncinate fasciculus decelerated as a function of mean p‐factor scores over the study period. This suggests that an increased expression of psychopathology is closely linked to lower rates of myelin maturation in selective brain tracts over time. Impaired myelin growth in limbic association fibres may serve as a neural marker for emerging mental illness during the course of adolescence and early adulthood.
Highlights
Abnormal neural connectivity due to structural changes in connecting white matter pathways is implicated in a wide range of psychiatric disorders including schizophrenia (Klauser et al, 2017; Kubicki et al, 2007), autism (Karahanoglu et al, 2018), depression (Tham, San Woon, Sum, Lee, & Sim, 2011), bipolar disorder (Nortje, Stein, Radua, Mataix-Cols, & Horn, 2013), obsessive–compulsive disorder (Brennan, Rauch, Jensen, & Pope Jr, 2013) and attention-deficit hyperactivity disorder (Nagel et al, 2011)
A significant effect of laterality indicated higher magnetisation transfer (MT) values in the right compared to the left hemisphere for the ATR, dorsal cingulum, hippocampal cingulum, inferior fronto-occipital fasciculus (IFOF) and ILF, and higher MT in the left compared to right hemisphere for the SLF and UF, all p
IFOF and ILF showed higher MT values in the right compared to the left hemisphere, whereas there were higher mean MT values in the left compared to the right UF, all ps
Summary
Abnormal neural connectivity due to structural changes in connecting white matter pathways is implicated in a wide range of psychiatric disorders including schizophrenia (Klauser et al, 2017; Kubicki et al, 2007), autism (Karahanoglu et al, 2018), depression (Tham, San Woon, Sum, Lee, & Sim, 2011), bipolar disorder (Nortje, Stein, Radua, Mataix-Cols, & Horn, 2013), obsessive–compulsive disorder (Brennan, Rauch, Jensen, & Pope Jr, 2013) and attention-deficit hyperactivity disorder (Nagel et al, 2011). Individual differences in white matter myelination may be a general risk factor for or an outcome of psychiatric disorders (Fields, 2008). The p-factor has been characterised in childhood (Martel et al, 2017) and early adolescence (Carragher et al, 2016; Patalay et al, 2015) through to early adulthood (Laceulle, Vollebergh, & Ormel, 2015; St Clair et al, 2017) It is reported as relatively stable throughout development (Murray, Eisner, & Ribeaud, 2016), capturing familial risk of psychopathology (Martel et al, 2017), and is thought to be subject to genetic regulation (Brikell et al, 2018; Neumann et al, 2016; Selzam, Coleman, Caspi, Moffitt, & Plomin, 2018). Structural connectivity within and between these networks, contingent on healthy development of white matter tracts, is of particular interest in this respect
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