Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort

Abstract

BackgroundChildhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.MethodsWithin the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.ResultsCM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.ConclusionsSeverity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Sex is a defining feature of neuroimaging phenotypes in major brain disorders

“…The ENIGMA-MDD working group confirmed these hallmarks in the largest subcortical, cortical, and white matter neuroimaging studies of MDD to date (N>8,000), yet none of these studies detected sex by diagnosis interaction effects on brain structure [Schmaal et al, 2016;Schmaal et al, 2017;van Velzen et al, 2019]. However, separate work by Frodl et al [2017] and Tozzi et al [2019] revealed sex by diagnosis interaction effects on subcortical and cortical brain structure as a function of childhood trauma exposure. In a meta-analysis of 3,036 participants (MDD=958, controls=2,078), greater severity of childhood trauma corresponded to smaller bilateral caudate volumes in females in both patient and control groups, but this effect was not significant in males [Frodl et al, 2017].…”

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

“…Capitalizing on the statistical power of ENIGMA to examine the role of risk factors, Frodl 74 and Tozzi 75 examined the association between retrospectively assessed childhood maltreatment (including emotional, physical and sexual abuse, or emotional and physical neglect), and brain morphometry in 3036 and 3872 individuals (aged 13-89) with and without MDD, respectively. Greater exposure to childhood maltreatment was associated with lower cortical thickness of the banks of the superior temporal sulcus and supramarginal gyrus, and with lower surface area across the whole brain and in the middle temporal gyrus.…”

“…Hibar et al 2,68 Volumetric reductions in hippocampus and thalamus and enlarged lateral ventricles in patients; thinner cortical gray matter in bilateral frontal, temporal and parietal regions; strongest effects on left pars opercularis, fusiform gyrus and rostral middle frontal cortex in BD. 67 ; Tozzi et al 75 ; Han et al 72 ; Frodl et al 74 ; Renteria et al 172 ;…”

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

“…Nonetheless, a recent longitudinal study showed that lower surface area was specifically observed in young people experiencing depressive symptoms in early adolescence but not in those developing depressive symptoms later in adolescence, and that lower surface area was already observable in young people with subclinical depressive symptoms, not all of whom will develop a fullthreshold MDD diagnosis 36 . Thus, cortical surface area reductions may represent an early developing subtype of depressive disorder, shaped by genetic factors or early life adversity (prenatal 73,74 or perinatal or during childhood [75][76][77], and potentially precede the onset of MDD. This hypothesis is consistent with the observation that, compared with cortical thickness, cortical surface area has a higher genetic heritability 27,64,78 , has a genetic correlation with MDD and depressive symptoms (this genetic association is absent for cortical thickness 27 ), is determined earlier in development, and is less strongly affected by later environmental influences 71,79 .…”

“…Two studies from the ENIGMA MDD consortium examined the effects of childhood maltreatment on brain structure in depressed and non-depressed individuals using a mega-analytic approach 75,110 . In the two largest studies to date examining associations between childhood maltreatment and brain structure, Frodl et al and Tozzi et al examined the association between severity of childhood maltreatment-including emotional, physical and sexual abuse, or emotional and physical neglect as assessed with the childhood trauma questionnaire (CTQ) -and brain morphometry in a total of 3036 and 3872 individuals with and without MDD, respectively.…”