Neurodegenerative and neurovascular diseases lead to heterogeneous brain abnormalities. A combined analysis of these abnormalities by phenotypes of the brain might give a more accurate... Show moreNeurodegenerative and neurovascular diseases lead to heterogeneous brain abnormalities. A combined analysis of these abnormalities by phenotypes of the brain might give a more accurate representation of the underlying aetiology. We aimed to identify different MRI phenotypes of the brain and assessed the risk of future stroke and mortality within these subgroups. In 1003 patients (59 +/- 10 years) from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, different quantitative 1.5T brain MRI markers were used in a hierarchical clustering analysis to identify 11 distinct subgroups with a different distribution in brain MRI markers and cardiovascular risk factors, and a different risk of stroke (Cox regression: from no increased risk compared to the reference group with relatively few brain abnormalities to HR = 10.34; 95% CI 3.80 <-> 28.12 for the multi-burden subgroup) and mortality (from no increased risk compared to the reference group to HR = 4.00; 95% CI 2.50 <-> 6.40 for the multi-burden subgroup). In conclusion, within a group of patients with manifest arterial disease, we showed that different MRI phenotypes of the brain can be identified and that these were associated with different risks of future stroke and mortality. These MRI phenotypes can possibly classify individual patients and assess their risk of future stroke and mortality. Show less
Abstract Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a... Show moreAbstract Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor: unresolved-disorganized attachment (Ud) resulting from loss or trauma. Methods: Unique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N = 63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N = 26) and without psychiatric disorder (N = 19). WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ. Results: Controlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. Conclusions: Decreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice. Keywords: Adversity, Child abuse, Psychopathology, Attachment, Brain imaging Show less
